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Full text of "Annual Report of International Activities 1981"

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Prepared by 
John E. Fogarty International Center 

for 
Advanced Study in the Health Sciences 



U.S. DEPARTMENT OF 

HEALTH AND HUMAN SERVICES 

Public Health Service 

National Institutes of Health 

NIH Publication No. 82-62 
September 1982 



NATIONAL INSTITUTES OF 

HEALTH 

ANNUAL REPORT OF 

INTERNATIONAL ACTIVITIES: 

FISCAL YEAR 1981 

TABLE OF CONTENTS 

Page 

Foreword v 

1. Highlights of Recent Scientific Advances 1 

2. Summary of International Activities by Country 5 

3. Fogarty International Center (FIC) 11 

4. National Cancer Institute (NCI) 23 

5. National Eye Institute (NEI) 35 

6. National Heart, Lung, and Blood Institute (NHLBI) 39 

7. National Institute on Aging (NIA) 53 

8. National Institute of Allergy and Infectious Diseases (NIAID) 55 

9. National Institute of Arthritis, and Digestive and Kidney Diseases (NIADDK) 67 

10. National Institute of Child Health and Human Development (NICHD) 71 

11. National Institute of Dental Research (NIDR) 75 

12. National Institute of General Medical Sciences (NIGMS) 77 

13. National Institute of Environmental Health Sciences (NIEHS) 79 

14. National Institute of Neurological and Communicative Disorders (NINCDS) 83 

15. National Library of Medicine (NLM) 85 

16. Clinical Center (CC) 89 

17. Division of Computer Research and Technology (DCRT) 91 

18. Division of Research Resources (DRR) 93 

19. Division of Research Services (DRS) 95 



in 



FOREWORD 



On behalf of the Director of the National Institutes of 
Health (NIH) and the staff of the Fogarty International 
Center for Advanced Study in Health Sciences (FIC), I 
am pleased to present this 13th National Institutes of 
Health Annual Report of International Activities. 
Edited by the FIC, but based upon reports by each of the 
Bureaus, Institutes, and Divisions (BID's) of the NIH, 
this report provides an overview of recent health- 
related international activities relevant to the NIH 
mission and within the purview of one or more of the 
BID's. 

The international programs of the NIH are autho- 
rized under the International Health Research Act of 
1960 (P.L. 86-610) to "advance the status of the health 
sciences in the United States and thereby the health of 
the American people through cooperative endeavors 
with other countries in health research, research 
planning, and research training. ..." But the benefits 
of NIH international programs extend far beyond our 
borders. Through cooperative relationships that the 
BID's have established in their intramural and extramu- 
ral programs, foreign biomedical and behavioral re- 
search scientists have collaborated with their U.S. 
counterparts to advance knowledge leading to im- 
proved methods of treatment, control, and, ultimately, 
prevention of disease. 

Since 1968, when the Fogarty International Center 
was created by the Congress, it has been the focal point 
for international facets of NIH activities. The number 
and kind of international programs differ from Institute 
to Institute, but the FIC is the only NIH component with 
an explicit international mission, which includes NIH- 
wide coordination of and liaison for activities relevant to 
this mission in addition to its specific international 
programs. 

The international activities of the NIH have many 
goals, dictated by the objectives of the intramural and 
extramural programs of the categorical Institutes and 
the resource and service Divisions. Implementation of 
these goals must in turn be responsive to and consistent 
with national and international policies. The coordina- 
tion and liaison functions of the Fogarty International 
Center are designed to serve as a resource for 
information from and to the Department of State, 
foreign embassies in this country, and multilateral 
organizations such as World Health Organization and 
Pan American Health Organization. At the same time, 
the international activities reflect changes in the health 
scene, as some diseases are reduced or controlled and 



others present new and broader challenges. The NIH is 
also concerned with the emerging needs of and 
opportunities in developing nations and has estab- 
lished contacts that are described in this report. 

As part of its coordinating function, the FIC was 
assisted by the BID's in providing the information for 
this report. A particular objective was that material be 
selected and presented in such a way that it would be 
useful for congressional purposes, would be of interest 
to scientists from abroad, and would provide specific 
examples of how international programs and activities 
have contributed to biomedical and behavioral research 
and national health in the U.S. It was also intended that 
information be conveyed in a fashion that would be 
intelligible to various audiences, including educated 
laymen, scientists who are not specialists in the area 
under discussion, and members of NIH councils and 
advisory groups. In a departure from past procedures, 
we asked the BID's to provide information under 
specific headings (for example, bilateral agreements, 
activities with international agencies). To present a 
relatively consistent format, we have taken some 
liberties with the reports submitted by the BID's. We 
have not altered the scientific material except to delete 
sections that were either not relevant to the goals of this 
report or were too detailed to be included. 

Chapter I of the report highlights scientific ad- 
vances resulting from recent collaborative efforts in- 
volving foreign and U.S. scientists. Chapter II provides 
information on a particular country, but does not 
include details which are covered elsewhere in the 
report. The remaining chapters were submitted by the 
BID's, but were edited for format and length. A table 
showing fiscal year 1981 total funding for NIH interna- 
tional programs is appended. 

Within the limitations of a single report it is not 
possible to do justice to the complexities of the NIH 
international activities and to their contributions to 
betterment of health in the U.S. and abroad. We are, 
nonetheless, endeavoring to provide a document of 
interest and use to a variety of audiences and welcome 
comments that will enable us to achieve these objec- 
tives. 



Mark S. Beaubien, M.D. 

Acting Director, Fogarty International Center 

Acting Associate Director, Office of International Research 

National Institutes of Health 



10-12-82 

FY 1981 Total Funding for NIH Inten 

($ in thousands) 
February 25, 1982 

I. Research Awards 

A. Grants: 

Regular Foreign Grants 3,1 

Special Foreign Grants (GMI, IPCS, ICIDR)* 
Domestic Grants with Foreign Components 1,( 

Special Foreign Currency (PL-480) Grants 

B. Contracts: 

Foreign Contracts 5, 

Domestic Contracts with Foreign Components 

II. Scientist Exchanges 

A. Foreign Scientists in U.S.: 

Visiting Associates, Scientists, Fellows 5,1 

International Research Fellowships 
Fogarty Scholars 

B. U.S. Scientists Abroad: 

Fogarty Senior Fellowships 
National Research Service Awards 
Foreign Work Study Assignments 

III. International Conferences 

IV. International Travel 

International Meetings 
Multilateral Organization Activities 
Bilateral Exchanges 
Other 

V. BID Program Support 

Bilateral Exchanges 
Staff and Other 

Totals 16,8 

Totals may not add due to rounding 



* GMI — Gorgas Memorial Institute 
IPCS — International Program on Chemical Safety 
ICIDR — International Collaboration in Infectious Diseases Rese; 



I 



10-12-82 



FY 1981 Total Funding for NIH International Programs — By Activity and BID 

($ in thousands) 
February 25, 1982 



I. Research Awards 

A. Grants: 

Regular Foreign Grants 

Special Foreign Grants (GMI, IPCS, ICIDR)* 

Domestic Grants with Foreign Components 

Special Foreign Currency (PL-480) Grants 

8. Contracts: 

Foreign Contracts 

Domestic Contracts with Foreign Components 

II. Scientist Exchanges 

A. Foreign Scientists in U.S.: 

Visiting Associates, Scientists, Fellows 
International Research Fellowships 
Fogarty Scholars 

B. U.S. Scientists Abroad: 
Fogarty Senior Fellowships 
National Research Service Awards 
Foreign Work Study Assignments 

III. International Conferences 

IV. International Travel 

International Meetings 
Multilateral Organization Activities 
Bilateral Exchanges 
Other 

V. BID Program Support 

Bilateral Exchanges 
Staff and Other 

Totals 



NCI 



3,836 

1,028 

225 

5,259 



5,162 



FIC NIADDK NHLBI NIAID NINCDS NICHD NIEHS NIDR NEI NIGMS NIA DRS NLM OC DCRT OD DRR Totals 



NIH 

Funds 



1,800 



3,450 
478 



2,078 

4 
648 

2,437 



909 

327 
26 

2,178 
235 



815 



932 

2,585 
160 



170 



876 



1,698 



129 



32 



1,536 



887 


290 


— 


400 


1,021 


26 


26 


227 



531 



825 



122 
31 



838 



399 
104 



7 — 
55 — 



741 



932 



366 



864 



903 



285 



405 



268 



131 



47 



90 



71 — 



Other 
Funds 



13,223 (13,223) 

I i (4,785) 

200 2,996 (2,996) 

911 ('M I) 

9,717 (9,717) 
267 (267) 



!4,5<,K (14,568) 

3,450 (3,450) 

478 (478) 



— 


673 


— 


— 








— 


— 


— 


— 


























673 


(673) 





54 
9 


— 


97 
56 


112 


44 


323 


62 


21 


55 
11 


58 


258 


46 


— 


— 


— 


— 


— 


— 


1,084 
120 


(1,084) 
(120) 


— 


138 


186 


138 


74 


140 


10 


18 


25 


6 


13 


15 


17 


3 


- 


5 


2 


8 


15 


SI l 


(811) 


- 


308 
34 
46 
90 


5 
2 
14 
9 


115 

11 

7 

39 


88 

3 

31 

23 


49 

6 

20 

11 


100 
19 
10 
4 


35 
17 
33 
28 


41 

11 

6 

39 


46 
3 

31 


14 

14 

24 

7 


2 


33 
9 

2 


1 

2 
15 
31 


3 

1 

3 
5 


4 


16 
3 


11 
6 
2 


3 


873 
137 
210 
322 


(467) 
(17) 

1 

(164) 


(406) 

(155) 

(101) 

(123) 


364 
270 


259 
2,232 


7 
90 


585 
196 


283 
83 


98 


26 
88 


42 
79 


81 


5 
12 


Z 


26 


27 
24 


188 


46 


- 


15 


- 


1,598 
3,528 


H, 198) 
(3,528) 


— 


,823 


9,108 


5,727 


5,602 


5,547 


4,045 


3,914 


2,437 


1,667 


1,410 


1,119 


1,041 


502 


309 


145 


92 


42 


218 


59,753 


(58,057) 


(1,696) 



totals may not add due to roundin 



1 'Ml I iorgas Memorial Institute 

lr ' s lniiTnjiiun.il I'm,;,,,,,, „„ Chemical Safer) 

l' IHK InternjtiiMuU oll.iboutkni in Infectious Diseases Research 



1. 



HIGHLIGHTS 

OF RECENT SCIENTIFIC 

ADVANCES 



The following highlights present a selective rather than 
exhaustive summary of scientific accomplishments 
under international research programs and activities 
sponsored by the Bureaus, Institutes, and Divisions 
(BID's) of the NIH. This summary has drawn upon 
detailed reports submitted by the BID's, but presents 
them in a different perspective. Whereas the BID's look 
at their international programs and activities in the 
context of their categorical missions, this section 
endeavors to view the accomplishments in the larger 
context of global health problems. In some instances, 
cooperative studies between the U.S. and other coun- 
tries are reported although they have not yet been 
completed or provided definitive answers. They are, 
however, important because they are using innovative 
research approaches or new technologies, or are 
studying special populations. Hence, they are opening 
new paths to the solution of health problems of 
international concern. 

Population studies are both difficult and costly to 
conduct in a fashion that provides reliable data and 
definitive answers. There are, however, populations in 
various parts of the world that have been valuable 
resources for the study of disease prevention and 
disease control using epidemiologic methods of inves- 
tigation. Through their international research pro- 
grams, the Institutes of NIH have engaged in coopera- 
tive epidemiologic studies with foreign countries when 
population groups provided features that were 
eminently suitable for learning about factors that cause 
or influence the course of a disease. In some instances, a 
population has been exposed to environmental factors 
rarely found elsewhere, or a population group with a 
uniform genetic background provides enough indi- 
viduals with a genetically determined disease to be 
suitable for an epidemiologic study. In still other 
instances, a population's ethnic background makes it 
possible to learn the influence of such factors as dietary 
habits, behavior patterns, and lifestyles on the inci- 
dence and prevalence of disease. Recent accomplish- 
ments resulting from such studies are highlighted 
below. 

A population study of interest is being conducted 
by NINCDS scientists in collaboration with scientists at 
the University of Zulia in Maracaibo, Venezuela. They 
are examining 200 patients with Huntington's disease 
and 2,000 of their relatives, because this population, 
descended from a single Spanish sailor who arrived in 



the country in 1860, offers an opportunity to study a 
neurologic disease known to be hereditary and present 
in an unusually large number of individuals. Although 
Huntington's disease occurs in the U.S., it is relatively 
rare. The disease is similar in its manifestations to more 
common neurologic disorders, including Parkinson's 
disease. The Venezuelan patients have been given 
neurologic and psychologic tests, and their movements 
have been recorded on film. The study is promising not 
only because it is a source of information about 
inherited neurologic disorders, but also because the 
population under study may include descendants who 
carry two genes for Huntington's disease as a result of 
intermarriage. 

In contrast to the genetic uniformity provided by 
the Venezuelan population is the population of Jeru- 
salem, which is of interest because of the diversity of 
ethnic backgrounds of its residents. There are, in 
consequence, great differences in dietary patterns, 
lifestyles, education, and socioeconomic status. The 
origin of the population has been accurately recorded. 
Among the young people, 90 percent are known to have 
been born in Israel, whereas only 20 percent of their 
parents were native born. This population, therefore, 
provides the opportunity to study the effects of diverse 
environmental factors on a disease and to assess various 
risk factors. Both NHLBI and NIADDK are cooperating 
with Israeli scientists in studies of this population as 
described below. 

The NHLBI, which has collaborated with many 
countries to collect data on environmental, familial, and 
genetic influences on atherosclerotic disease, has 
supported the establishment of a Jerusalem Lipid 
Research Clinic at Hadassah University Hospital that 
capitalizes on the resource available in the multiethnic 
population of Jerusalem. The study has screened more 
than 8,000 young people as part of their preinduction 
examination for military service, and about 7,000 of 
their parents. Preliminary data show important differ- 
ences in dietary fat intake and blood lipid profiles that 
correlate with differences in the country of parental 
origin. The results thus far also provide clues to the 
relative roles of genetic factors and lifestyle in the 
etiology of cardiovascular disease. Of great interest is 
that Yemenites migrating to Israel suffered from 
malnutrition but not from diabetes or heart disease; but 
after a single generation on an Israeli diet, Yemenites 
began to develop both of these diseases. The fact, 



1 



however, that they did not develop diabetes or heart 
disease to the extent it developed in Israelis of European 
parentage indicates that genetic as well as environmen- 
tal influences are involved. 

Another study taking advantage of the opportunity 
to study the effect of dietary components on the 
manifestations of a disease in persons with different 
ethnic backgrounds is being conducted in Jerusalem by 
the Hebrew University of Jerusalem with support by 
NIADDK. The effects of prolonged administration of a 
combination of calcium, phosphate, and fluoride salts 
on bone density and structure are being studied in a 
middle-aged group of patients with osteoporosis. 

Using funds available through the FIC Special 
Foreign Currency Program, the NHLBI is sponsoring a 
study in Poland with the Polish Academy of Sciences to 
determine the extent to which the main risk factors for 
coronary heart disease can be reduced in industrial 
workers. Preliminary data indicate higher blood pres- 
sure and cholesterol values in Warsaw than in Cracow, 
and a higher prevalence of cigarette smoking than in the 
U.S. Compared with the U.S., the Polish workers are 
more obese and have about the same prevalence of 
hypertension and considerably lower cholesterol levels. 

A recent report of a collaborative study by NCI and 
Japanese scientists is another example of how a disease 
in a population group in a given locale may provide 
opportunities for research not possible in other popula- 
tions. In this study, antibodies against an RNA tumor 
virus (retrovirus) were found in the blood of Japanese 
patients with adult T cell lymphoma but not in the blood 
of healthy persons from the same region or other parts 
of Japan. The type of T cell lymphoma under study 
occurs in fewer than 1 percent of all types of leukemia 
patients in the U.S. but is endemic in southwestern 
Japan, where it occurs in striking clusters on the islands 
of Kyushu and Shikoku. Antibodies to a virus have 
previously been demonstrated in animals with leuke- 
mia, but this is believed to be the first time such a 
relationship has been shown in human leukemia. These 
observations are not only of theoretical interest in 
relation to the etiology of cancer, but are also of possible 
clinical importance if a vaccine against the virus can be 
developed. 

Although for most diseases epidemiologic studies 
reveal striking differences in incidence and prevalence 
in different geographic regions, this is not the case for 
one of the devastating alterations associated with aging; 
namely, Alzheimer's disease (senile dementia). A 
WHO world study has shown that about 6 percent of 
persons above age 65 are affected, and the prevalence is 
surprisingly consistent in different countries. The NIA 
and NINCDS have an interest in this disease and are 
examining the causes of the disability and the progres- 
sive degenerative changes that occur in populations in 
Canada, Holland, and Denmark. New test batteries 
have provided a finer dissection of cognitive versus 
memory disorders. Clinical, neurophysiological, 
biochemical, histopathological, and radiographic char- 
acteristics are being examined to determine the rela- 
tionship between pathological changes and clinical 
manifestations. Some studies are concerned with 
regional alterations in brain metabolism that occur in 



Alzheimer's disease, but thus far measurements have 
been made only on normal subjects. 

An NEI epidemiologic study in Egypt that address- 
ed prevention of blindness caused by trachoma, which 
is caused by an infectious agent (Chlamydia) found in the 
nose, throat, and feces, is also relevant to the interests 
of NIAID, because the same causative agent is associ- 
ated with diarrheal disease and bronchitis in children. 
This type of blindness is more prevalent in Egypt than' 
in countries of Western Europe and North America . The 
infectious agent is present in about 4.7 percent of the 
rural and 1.7 percent of the urban population of Egypt, 
but in no more than 0.2 percent of the population in the 
U.S. and Europe. When children are treated with 
antibodies against the infectious agent, and when 
hygienic measures are improved, trachoma as well as 
diarrheal disease and bronchitis are prevented. 

NCI and NIAID have been sponsoring studies of a 
relationship between viral hepatitis and liver cancer 
(hepatoma), a relationship uncovered through 
epidemiologic studies in China (Taiwan), where hepa- 
toma is the leading cause of death in males. Risk of 
developing this form of cancer was 340 times greater 
among carriers of hepatitis virus than among noncar- 
riers, and 80 percent of patients with liver cancer 
showed the presence of hepatitis virus antigen. NIAID 
is supporting a clinical trial in China (Mainland) to 
assess the efficacy of a vaccine (developed in the United 
States) in preventing transmission of hepatitis virus to 
the neonate by mothers who are carriers. Because 
infected children are at risk of developing liver cancer in 
later life, the trial has important implications for the 
prevention of hepatoma. This is a problem of world- 
wide dimensions. Viral hepatitis affects almost one- 
half million persons in the United States, and 5 to 10 
percent of these become carriers of the virus. In some 
parts of Southeast Asia and South Africa, as many as 
one in five persons test positive for the viral antigen. 
The array of Federal agencies that participated in this 
activity attests to the importance of this infectious 
disease and its relationship to other health problems. 
Sponsors of the International Symposium on Viral 
Hepatitis included the NIH Clinical Center and Blood 
Bank, the CDC, FDA, and NIAID, NCI, and FIC. 

Among exogenous agents implicated in disease, 
nutritional factors have a pervasive role that is evident 
in reports of a number of Institutes. In some instances, 
dietary influences on a given disorder can be readily 
corrected once the critical factor has been identified. A 
noteworthy example is a reduction of bladder stone 
disease in children following identification of a nutri- 
tional deficiency. In Northeast Thailand, as in many 
developing countries, bladder stone disease is endemic 
in children, beginning as early as 1 year of age and 
peaking by age 3. An epidemiologic study of 21,000 
individuals in this region of Thailand revealed oxalate 
crystalluria alone or with uric acid crystalluria in all age 
groups, but especially in children under 45 days. It 
occurred in 43 percent of these children, who also 
excreted very little phosphate in their urine. When an 
orthophosphate supplement was given in a small trial, 
the oxalate crystalluria disappeared within 24 hours in 



children aged 6 to 19 months. In a subsequent more 
extensive 5-year trial supported by NIADDK, phos- 
phated soda pop given 1,200 Thai infants and preschool 
children has led to a 60 percent reduction in bladder 
stone disease. 

The role of nutrition in the control of hypertension 
and its sequelae has been the focus of a U.S. -Japanese 
study for some years. The importance of hypertension 
in the U.S. has been well documented through the 
NHLBI prevention program. In Japan, hypertension as 
a cause of stroke, which is a prevalent disease, is also of 
concern. Animal models developed in Japan have been 
useful tools for nutritional studies. A rat model of 
hypertension is available in the spontaneously 
hypertensive rat, and more recently, a stroke-prone 
spontaneously hypertensive rat model has been de- 
veloped. Using the stroke-prone rat model, Japanese 
researchers have found a stroke-preventive effect of a 
dietary protein fed to animals with severe hyperten- 
sion. The stroke-prone, spontaneously hypertensive rat 
had a lower incidence of stroke when fed the NIH rat 
diet than when given the standard Japanese diet. The 
protein to which the stroke-prevention effect is attri- 
buted includes sulfur-containing amino acids and 
certain aromatic amino acids. To be effective, the 
dietary intervention must be during the 3rd to 6th 
month of the animal's life, which is equivalent to ages 15 
to 20 in man. There is now epidemiologic confirmation 
of the importance of dietary proteins in the develop- 
ment of stroke in Japanese population studies. 

The interplay between scientific advances in the 
United States and abroad is well illustrated by some of 
the anticancer agents undergoing trials supported by 
NCI. Aclacinomycin A, an agent developed in Japan, 
has been shown to have good activity against leukemias 
and lymphomas (but not against solid tumors). It has 
undergone a Phase I (toxicity) trial and is now being 
studied in a Phase II (dosage) trial. Teroxirone, an 
anticancer agent that appears to be active against a 
variety of cancers, is undergoing a Phase I trial. Two 
analogs of anticancer agents (Adriamycin and Dauno- 
rubicin), produced by Italian scientists, are now 
undergoing preclinical testing because they appear to 
have less cardiotoxicity and to be active in a broader 
range of tumor systems than the agents now in use. 

In a cooperative study by U.S. and Italian scien- 
tists, a device developed in the United States to aid in 
the treatment of acute respiratory distress syndrome is 
undergoing a clinical evaluation in both countries. 
Adult patients suffering from the usually fatal respira- 
tory distress syndrome are being treated with an 
extracorporeal device that removes carbon dioxide, 
bringing the lung to rest, but allowing enough oxygen 
to diffuse through the motionless lung to maintain 
adequate oxygenation. Called "apneic oxygenation," 
the technique has shown sufficient promise in prelimi- 
nary studies to warrant further exploration as a device 
to keep the patient alive until the lung has recovered 
sufficiently to resume its respiratory function. 

Several recent studies exemplify how basic re- 
search can contribute to the clinical aspects of a disease 
problem. NIEHS and NCI scientists, in collaboration 
with scientists throughout the world, have developed 



and validated 30 different short-term bacterial mutation 
test systems. This is of clinical importance because 
environmental agents capable of altering DNA within 
cells may have carcinogenic as well as mutagenic 
effects. Because it may be decades before a cancerous 
lesion due to an environmental agent has reached 
detectable dimensions, a test that can discriminate 
between carcinogens and noncarcinogens is of practical 
value. It also has implications for hereditary diseases 
because it detects DNA damage. The problem is 
complex because a number of factors are known to 
interact in determining the ultimate action of chemical 
mutagens and carcinogens. An example of such a factor 
is diet, as has been shown in a U.S. -Japanese coopera- 
tive study in which mutagenic and carcinogenic 
compounds have been identified and isolated from 
fried sardines and beef that have undergone alterations 
in the cooking process. 

A U.S. -Chinese study of liver cancer supported by 
NCI provides another example of a basic study that may 
contribute to solution of a clinical problem: early 
detection of a disease. The investigation has drawn 
upon the availability of monoclonal antibodies, an 
availability that has resulted from dramatic recent 
advances in hybridoma technology. The study was 
triggered by the observation that aflatoxin, a toxic 
substance produced by a fungus (Aspergillus) that 
grows on peanuts and grains, is abundant in areas 
where liver cancer is prevalent. 

Monoclonal antibodies to aflatoxin B ( and aflatoxin 
B r adducts are being used to assess the effects of 
aflatoxin on cell metabolism and DNA damage in 
Chinese populations known to be at high risk of 
developing liver cancer. It is anticipated that antibodies 
to aflatoxin and its DNA adduct will be a useful 
biochemical marker of liver cancer and may contribute 
to earlier detection of this disease. 

In a collaborative U.S. -Norwegian study of succes- 
sive pregnancies, the NICHD reports that there is an 
association between perinatal mortality rates and the 
general tendency to repeat similar outcomes in succes- 
sive pregnancies. For example, an underweight infant 
born to a woman who previously had given birth to a 
baby of normal size is at higher risk of perinatal death 
than an underweight infant born to a woman whose 
first infant was also underweight. 

Although biomedical advances often have their 
inception in other countries, the U.S. is usually more 
conservative about adopting seemingly promising 
procedures until they have been clearly demonstrated 
to be both effective and without unwarranted or 
excessive side effects that are hazardous. An example is 
the trial being mounted in the U.S. to assess the efficacy 
of radial keratotomy, a surgical procedure to correct 
myopia that originated in the U.S.S.R. and is now being 
used in the U.S. with increasing frequency. Brought to 
this country by a physician who learned the procedure 
in the Soviet Union and trained others in its use, the 
procedure is now being assessed in a clinical trial 
supported by NEI to determine whether the reported 
beneficial effects persist, and whether damaging effects 
may manifest themselves later. 



2. 



SUMMARY 
OF INTERNATIONAL ACTIVITIES 

BY COUNTRY 



The NIH had some type of activity with 70 countries 
throughout the world in fiscal year 1981 through 
fellowships, grants, contracts, visiting scientists, and 
special foreign currency. This chapter summarizes 
activities for those countries with which there are 
formal bilateral agreements and for those with which 
there are a large number of informal scientific rela- 
tionships. It is not intended to be a comprehensive 
description, of either the activities or the countries. 

Argentina 

A Science and Technology Agreement administered by 
the National Science Foundation is in effect. The 
Argentine Minister of Health designate visited NIH in 
February 1981 and discussed collaboration on research 
in Chagas' disease and coronary artery disease. 

Australia 

Although there is no formal agreement for collaboration 
with Australia, the following Institutes carry out 
cooperative programs with that country: DCRT, 
NIEHS, NICHD, NIDR, NIADDK, NEI, NIAID, NCI, 
NIGMS, and FIC. Australia is among the top 10 
countries that successfully compete for NIH awards. 

Brazil 

An overall science and technology agreement was 
signed in 1971. There is no formal DHHS agreement. 
However, there have been useful relationships with 
Brazilian scientists and institutions over the years. The 
following Institutes participate in collaborative pro- 
grams with Brazil: NLM, DRS, NIAID, NCI, and FIC. 

Major activities being carried out in Brazil are: 
•PAHO Regional Library of Medicine (BIREME) in Sao 
Paulo (NLM). 

•Agreement between PAHO and Brazil to establish 
primate breeding and conservation programs (DRS). 
•International Collaboration in Infectious Diseases 
(ICIDR) Program, consisting of various collaborative 
projects under the science and technology agreement 
between Brazil and U.S. institutions funded by NIAID. 
•Collaboration with PAHO and BIREME in Latin 
American Cancer Information Project (NCI). 
•Two NCI-PAHO Collaborative Cancer Treatment 
Research Centers in Rio de Janeiro and Sao Paulo. 



Canada 

Although there is no formal bilateral agreement with 
Canada, there is a great deal of interaction between NIH 
and Canadian scientists. Canada has been the recipient 
of more NIH awards than any other foreign country. FY 
1981 awards exceeded $8 million. The following 
Institutes support research projects in Canada: DCRT, 
NHLBI, NIEHS, NCI, NEI, NICHD, NIADDK, 
NINCDS, NLM, NIGMS, NIAID, NIA, NIDR, and FIC. 

Egypt 

An overall health agreement provides for a U.S. -Egypt 
Joint Working Group on Health Cooperation. Coopera- 
tive projects are being carried out in epidemiology and 
control of streptococcal infections; schistosomiasis; viral 
and posttransfusion hepatitis; microbiologic con- 
tamination of foods; laboratory management tech- 
niques in health care; and studies of bladder cancer. The 
following Institutes are involved in collaboration with 
Egypt: NLM, NIEHS, NCI, NINCDS, NICHD, NEI, and 
NIAID. Of particular interest to NIH is the high 
incidence of hepatitis, bladder cancer, schistosomato- 
sis, and leishmaniasis, all of which provide opportuni- 
ties for research not available in the U.S. 

The following accomplishments have been re- 
ported: 

•Completion of a joint project of population screening 
for urinary bladder cancer by urinary cytology in an 
endemic area of schistosomiasis (NCI). 
•AID-funded program established by NIAID on malar- 
ia, Rift Valley fever, and leishmaniasis involving U.S. 
and Israel with Egypt. 

Federal Republic of Germany 

Bilateral relationships in the health field with the 
Federal Republic of Germany (FRG) are conducted 
under the agreement between DHHS and the Ministry 
of Research and Technology (MORT) of the FRG, 
commencing September 1976. A renewal of this agree- 
ment was discussed in July 1981 in Bonn. Participating 
Institutes are NCI, NHLBI, and FIC. 

Highlights of recent accomplishments are: 
•Cancer research activities in the fields of autovalent 
cytology, cytochemistry, and computer analysis. 
•Development of a joint protocol for drug development 
and a testing program for cancer treatment. 



•A joint workshop on Multiple Risk Factor Intervention 
Trials in cardiovascular disease held April 1981 in the 
FRG. 

•U.S.-FRG Workshop in Bethesda to discuss coopera- 
tive activities relative to the German National Health 
survey as it relates to cardiovascular disease. 

Finland 

A draft Memorandum of Understanding between 
DHHS and the Finnish Ministry of Social Affairs and 
Health is under review. 

France 

The following agreements with France govern coopera- 
tion between the two countries: NIH-INSERM Agree- 
ment — exchange of letters between the Director of the 
NIH and LTnstitut National de la Sante et de la 
Recherche Medicale (INSERM) for cooperation in the 
biomedical sciences (1969); NCI-INSERM Agreement 
for expanded cooperation in cancer research (1975); 
NLM-INSERM Agreement for on-line bibliography 
data bases (1974); NIH-French National Center for 
Scientific Research (CNRS) Agreement for support of 
exchange visits of scientists (1978). Both the INSERM 
and CNRS awards are administered by FIC. Institutes 
that participate in activities with France are NCI, 
NHLBI, NIADDK, NLM, and FIC. 

The following accomplishments have been re- 
ported: 

•Research progress in the area of pulmonary interstitial 
disorders (NHLBI). 

•Basic and clinical research studies (NCI). 
•Continued cooperative study of structure and mecha- 
nics of thyroid hormones (NIADDK). 
•Agreement that scientist exchange under the NIH- 
CNRS accord was mutually beneficial. 
•One Scholar-in-Residence (FIC). 

Greece 

An agreement for cooperation in science and technolo- 
gy was signed April 22, 1980. Under this agreement, a 
working group on scientific and technological coopera- 
tion was established. At the first meetings on October 
2-3, 1981, the U.S. agreed to explore the interests of its 
agencies in holding joint symposia with Greek counter- 
parts on one or all of the following topics: 
•Nutritional factors in disease (e.g., cardiovascular, 
cancer). 

•Emergency health services. 

•Molecular biologic aspects of malignant neoplasia. 
•Congenital hemoglobinopathies. 

Hungary 

An agreement between the Governments of the 
Hungarian People's Republic and the U.S. on Coopera- 
tion in Culture, Education, Science, and Technology 
was signed April 6, 1977. A Memorandum of Under- 
standing with NCI for a cooperative cancer program 
was signed February 23, 1981. Priority areas are 
epidemiology, experimental pathology, immunology, 



and therapy. NCI, NHLBI, and NINCDS have or are in 
the process of developing Institute-to-institute or 
project-level relationships under the framework of the 
U.S. -Hungary Agreement. The Hungarian Govern- 
ment has agreed to the exchange of individual health 
scientists at a level of 12 man-months per year for each 
side. 

India 

An overall science and technology agreement with 
India is implemented by the Scientific Working Group 
on Medical and Health Sciences of the Indo-U.S. 
Sub-Commission on Science and Technology. The 
following cooperative projects are being carried out: 
determination of the safety and efficacy of contraceptive 
measures; increased understanding of the relationship 
between nutrition and blindness and the means of 
preventing blindness; and improving methods for 
preventing and treating filiarisis. The following Insti- 
tutes participate: NICHD, NLM, NEI, NCI, NINCDS, 
NIAID, NIA, NIADDK, DRR, and FIC. 

Highlights of accomplishments are listed below: 
•Agreement to establish a Center for Research on 
Nutritional Blindness in Hyderabad. 
•Joint workshop on "Reproduction and Contraceptive 
Research" held in Bethesda. 

•Establishment of a Reagent Bank for Reproductive 
Biology Research in India. 

•Development and testing of new contraceptives. 
•Strengthening of capabilities for research in clinical 
epidemiology. 
•Hybridoma workshop. 

•DRS senior staff member assigned to U.S. Embassy in 
New Delhi to assist the Science Counselor in health 
issues. 

Israel 

The U.S. -Israeli Binational Science Foundation was 
created to pool the remaining U.S. Special Foreign 
Currency resources and matching Israeli funds when 
Israel was removed from the "excess foreign currency" 
list. NIH provides technical opinion on research 
projects submitted to the Foundation for funding. A 
U.S. -Israel Health Agreement was signed in 1980. 
Priority areas will be established in the near future. 
Israel's high level of scientific development and excel- 
lent institutions are conducive to very productive 
scientific collaboration. The following Institutes have 
established collaborative projects with Israel: NHLBI, 
NIADDK, FIC. 

Recent accomplishments are: 
•Establishment of Lipid Research Clinic in Israel by 
NHLBI. 

•Cooperative study by NIADDK on bone diseases. 
•Five Scholars-in-Residence. 

•U.S. AID-funded program established on malaria, Rift 
Valley fever, and leishmaniasis involving U.S., Egyp- 
tian, and Israeli scientists. 

Italy 

There are two separate agreements with Italy for 



cooperation in science and technology. Collaborative 
areas are biomedical communications; health aspects of 
environmental pollution; cardiovascular diseases; U.S.- 
Italy cancer program; cell biology and immunology; and 
mental health. The following Institutes participate in 
the agreements: NLM, NIEHS, NHLBI, NCI, and 
MAID. 

Accomplishments that have been reported are: 
•Workshop on "Clinical Biomedical Pharmacology," 
November 1980, on opportunities for collaborative 
studies. 

•Symposium on "Nutrition and Cardiovascular Dis- 
ease," December 1980, explored role of nutrition in 
development and prevention of cardiovascular disease. 
•U.S. -Italy Joint Committee meeting held in Bethesda, 
November 1980. 

•Partial support by NCI of Coordinating Center for 
Melanoma, National Institute of Oncology, Milan. 

Japan 

Bilateral relationships with Japan in the health field are 
encompassed under several distinct agreements or 
arrangements: U.S. -Japan Cooperative Medical Science 
Program (JCMSP); U.S. -Japan Cooperative Cancer 
Research Program; U.S. -Japan Cooperative Program on 
Vision Research; U.S. -Japan Program for Science and 
Technology (Non-Energy) Cooperation; and Agree- 
ment between the U.S. National Library of Medicine 
and the Japan Information Center for Science and 
Technology for input to the NLM MEDLARS data bank. 
Institutes participating in the agreement are NCI, 
NHLBI, NIAID, NEI, NIADDK, NIEHS, DRS, NLM, 
and FIC. 

Some accomplishments under these relationships 
are: 

•Seventeenth Meeting of the Joint Committee of the 
U.S. -Japan Cooperative Medical Science Program held 
in July 1981. 

•Publication of a third 5-year report on the U.S. -JCMSP 
(1975-80). 

•Identification of specific areas of mutual interest 
related to recombinant DNA research. 
•A handbook, near completion, on genetic monitoring 
of laboratory animals. 
•One Scholar-in-Residence. 



Kenya 

A Memorandum of Understanding for Scientific and 
Technical Cooperation was signed in September 1980, 
and the areas of cooperation related to it will be 
identified in the future. 



Kuwait 

A bilateral agreement between DHHS and the Ministry 
of Public Health of Kuwait for Technical Cooperation 
Programs in Health was signed May 8, 1981. The 
agreement is primarily a vehicle by which Kuwait 
would obtain technical services or consultation from the 
U.S. on a reimbursable basis. In the only activity in FY 



1981, NHLBI was requested to provide names of 
consultants for a program to be developed in hyperten- 
sion prevention and control. 

Mexico 

There is no formal bilateral agreement with Mexico. A 
joint communique was signed in 1981 for the continua- 
tion of the U.S. -Mexico Border Initiative, but NIH has 
not participated in this as yet. The NINCDS and the 
Institute of Neurology, Mexico City, are both WHO- 
designated Collaborating Centers for Research and 
Research Training in the Neurological Disorders. A 
collaborative protocol has been established between the 
two institutions for research and research training in the 
areas of epilepsy and stroke. Additionally, a small pilot 
program in neuroimmunology has been established. 

Nigeria 

A Memorandum of Agreement for Health Cooperation 
was signed in 1981, under which Nigeria will reimburse 
the U.S. for projects that are of benefit to Nigeria. 
Cooperation in the following areas has been proposed: 
tropical diseases; cancer; cardiovascular disease; 
hemoglobin disorders; and dental/oral diseases and 
nutrition. There is interest on the part of many 
Institutes, and plans are being formulated. NIEHS and 
National Institute of Occupational Safety and Health 
will share responsibility for cooperation in environmen- 
tal and occupational health. The first meeting of the 
Joint Working Group on Health Cooperation was held 
in February 1981. 

People's Republic of China 

The U.S.-PRC Protocol for Cooperation in the Science 
and Technology of Medicine and Public Health has 
been in effect since June 1979. Cooperative projects 
have been established in infectious and parasitic 
diseases; cancer; cardiovascular diseases; public health 
and health services research; child health and nutrition; 
environmental and occupational health; medical in- 
formation science; immunology; medical genetics; men- 
tal health; food and drugs, including pharmacology; 
and reproductive physiology and family planning. 
Institutes participating in the protocol are NCI, NHLBI, 
NIAID, NICHD, NIEHS, and NLM. 

The following accomplishments have been re- 
ported: 

•The second Joint Health Committee Meeting in 
Tianjin, China, November 1980. 
•Agreement to test hepatitis B vaccine in China. 
•Agreement to conduct a major epidemiologic study of 
cardiovascular disease in selected populations in China. 

Poland 

Under a bilateral agreement between the Governments 
of the U.S. and the Polish People's Republic, on 
Cooperation in the Field of Health, signed in October 
1974, a joint oversight committee (DHHS and Polish 
Ministry of Health) approves health projects supported 



7 



by the Joint Fund for Science and Technology. These 
activities are a followup to Special Foreign Currency 
projects. A U.S. -Poland Individual Health Scientist 
Exchange Program is administered by FIC on behalf of 
Public Health Service (PHS) agencies. 

There is scientific collaboration on more than 30 
projects in the health field. Participating Institutes are 
NHLBI, NICHD, NLM, NIADDK, NINCDS, and FIC. 
There are 13 institute-to-institute agreements involving 
both Federal and non-Federal health research institu- 
tions. 

Listed below are highlights of U.S. -Polish col- 
laboration. 

•Symposium on "Ischemic Heart Disease," arranged 
jointly by the National Institute of Cardiology, Warsaw, 
and the NHLBI, March 1981, in Bethesda. 
•Agreement for Cooperation in Cancer Research be- 
tween NCI and the Maria-Sklowdowska-Curie Memo- 
rial Institute of Oncology, renewed in April 1981. 
•Fifth Annual U.S. -Polish Medical Week, held October- 
November 1980 in Bethesda, focused on pediatrics. 
Visiting delegation led by representatives from the 
National Research Institute for Mother and Child, 
Warsaw. 

Romania 

An agreement between the Government of the United 
States of America and the Government of the Socialist 
Republic of Romania on Cooperation and Exchanges in 
the Cultural, Education, Scientific and Technological 
Fields was signed December 13, 1974. Joint workshops 
conducted at NIH in 1979 and in Romania in 1980 
identified immunology and metabolic activity as they 
relate to cancer and cancer-causing agents as areas for 
future collaboration. 

The U.S. -Romania Individual Health Scientist 
Exchange Program, administered by FIC for all PHS 
agencies, falls under the agreement for science and 
technology, and sponsors exchange visits of health 
scientists. 

Spain 

A complementary agreement on scientific and tech- 
nological cooperation with Spain is expected to be 
signed in the near future. The Public Health Service has 
sent an expert team to Spain to consult with Spanish 
authorities on health problems associated with chemi- 
cally contaminated cooking oil. 

Sweden 

NIH research relationships with Sweden have been 
close and active over many years, although there is no 
formal cooperative agreement. The high quality of 
biomedical institutions and investigators in Sweden 
and the openness of their international relationships 
have allowed for this degree of interchange without the 
need for formal agreement. Sweden has ranked among 
the four or five countries most successful in competing 
for NIH awards. Sweden offers five or six research 
fellowships each year to young U.S. scientists for work 
in Swedish laboratories; FIC screens and nominates the 



fellowship candidates. The following Institutes make 
awards to Swedish scientists and institutions: NCI, 
NIA, NIADDK, NIDR, NINCDS, NHLBI, NEI, and 
FIC. 

Switzerland 

While there is no formal agreement for cooperation 
between the NIH and Switzerland, there is frequent 
and active collaboration. Switzerland ranks within the 
top 10 countries competing successfully for NIH 
awards. Switzerland offers fellowships to promising 
U.S. scientists for study in Switzerland; FIC screens and 
nominates candidates. The following Institutes make 
awards to Swiss scientists and institutions: NIAID, 
NCI, NEI, NIADDK, DCRT, NIDR, and FIC. 

Taiwan 

Under the Taiwan Relations Act (P.L. 96-8, 1979), the 
American Institute in Taiwan (U.S.) and the Coordina- 
tion Council for North American Affairs (Taiwan) 
signed the Cooperative Science Agreement on Septem- 
ber 4, 1980. The Division of International Programs, 
National Science Foundation, accepted the leading role 
in promoting scientific and scholarly cooperation on 
January 27, 1981. There are currently no cooperative 
projects. However, in FY 1981, one Taiwanese scientist 
was a Fogarty Scholar-in-Residence. 

Union of Soviet Socialist Republics 

Cooperation between NIH and counterpart agencies in 
the Soviet Union takes place under three agreements: 
Agreement for Cooperation in Medical Science and 
Public Health, Agreement for Cooperation in Artificial 
Heart Research and Development, and Agreement for 
Cooperation in the Field of Environmental Protection. 
An individual health scientist exchange program with 
the Soviet Union is administered by FIC for the Public 
Health Service. 

The following accomplishments have been re- 
ported: 

•Testing and evaluation of Soviet anticancer drugs by 
U.S. scientists. 

•Collection of information on risk factors contributing 
to cardiovascular disease and on treatment of advanced 
coronary heart disease. 
•Testing of artificial heart devices. 
•Joint clinical trials using Soviet-developed Q-switched 
laser in treatment of glaucoma. 

•Exchange of information and virus isolates enabled 
U.S. public health specialists to prepare better for 
influenza epidemics. 

•Information on possible health impacts of oil shale 
production and electromagnetic radiation effects was 
made available to U.S. scientists. 

United Kingdom 

Although there is no formal agreement for cooperation 
with the United Kingdom, there is frequent and active 
cooperation between scientists. NCI, NHLBI, and FIC 
have collaborative programs with the United Kingdom. 



Some recent accomplishments are: 
•Cooperation between NHLBI and Britain in the 
development of a computer-based chemical informa- 
tion system; the British-Norwegian Migrant Study to 
assess the prevalence of "angina" and other cardiores- 
piratory symptoms; and the European Trial in Multi- 
factorial Prevention of Coronary Heart Disease. 
•Cooperative preclinical and clinical research associa- 
tions between U.S. and U.K. cancer centers, stimulated 
by and with partial support from NCI. 
•One Scholar-in-Residence. 

Venezuela 

An agreement for Scientific and Technological Coopera- 
tion in Health between DHHS and the Venezuelan 
Ministry of Health was signed August 11, 1980. The 
following cooperative projects are planned: systems for 
maintenance of scientific equipment and research on 
infectious diseases including leprosy, Chagas' disease, 
diarrheal diseases, and cardiovascular diseases. NIAID, 
DRS, FIC, NHLBI, and NINCDS have or plan to carry 
out programs with Venezuela. 

Yugoslavia 

An agreement between the Governments of the U.S. 



and the Socialist Federal Republic of Yugoslavia on 
Scientific and Technological Cooperation was signed 
May 18, 1973. The agreement established the U.S.- 
Yugoslavia Joint Board on Scientific and Technological 
Cooperation and Joint Fund administered by the Board. 
An individual health scientist exchange program is 
supported by the Joint Fund and administered on the 
U.S. side by FIC. The following Institutes have ongoing 
collaborative programs with Yugoslavia: NLM, NHLBI, 
NINCDS, NICHD, and FIC. 

The following accomplishments have been re- 
ported: 

•Long-term prospective study of cardiovascular disease 
in a large population of Yugoslav men supported by 
NHLBI. Six joint publications have resulted. 
•Epidemiologic followup study of secular trends on 
coronary heart disease risk factors in Yugoslavia. 



Zimbabwe 

A Science and Technology Agreement was signed in 
September 1980, under which NIH initiated discussions 
with the Zimbabwe Ministry of Health for cooperation 
in biomedical research. 



3 



JOHN E. FOGARTY 

INTERNATIONAL CENTER FOR 

ADVANCED STUDY 

IN HEALTH SCIENCES 



Introduction 

The Fogarty International Center (FIC) was created by 
an act of Congress in 1968 to provide a focus and an 
organizational mechanism for the role of NIH in 
international cooperation in all aspects of biomedical 
research. 

The mission and objectives of the Fogarty Interna- 
tional Center are to: 

•Provide the facility for the assembly of scientists and 
leaders in the biomedical, behavioral, and related fields 
for discussion, study, and research relating to the 
development of science internationally as it pertains to 
health and its implications and applications for the 
future. 

•Further international cooperation and collaboration in 
the life sciences through its research programs, confer- 
ences, and seminars. 

•Provide postdoctorate fellowships for training in the 
United States and abroad and promote exchange of 
senior scientists between the United States and other 
countries. 

•Coordinate the NIH activities and functions generally 
concerned with the health sciences at an international 
level. 

•Serve as a focal point for foreign visitors to the 
National Institutes of Health. 

In addition to the conduct of its particular prog- 
rams, the FIC serves a central coordinating and 
integrating function for the international aspects of 
biomedical and behavioral research of the NIH, and as a 
major source of advice to the NIH Director on all matters 
related to international health. The Center maintains 
liaison with other components of DHHS, the Depart- 
ment of State and other Federal agencies, foreign 
embassies, and multinational and foreign organiza- 
tions. On international issues and activities, the FIC 
must interact with each of the major Bureaus and 
Institutes of NIH as well as other cross-cutting Bureaus, 
Institutes, and Divisions. The Director, FIC, represents 
the Director, NIH, in providing policy guidance to, and 
participating with, the Institutes in the negotiation of 
formal agreements of cooperation with other govern- 
ments and international organizations. 

The FIC carries out its mission under five pro- 



grams: the Advanced International Studies Program; 
International Research and Awards Programs; NIH 
Foreign Scientists Assistance Program; Special Foreign 
Currency and Joint Fund Programs; and International 
Coordination and Liaison Program. It also provides 
core support for the Gorgas Memorial Laboratory in 
Panama. These programs and activities for FY 1981 are 
described below. 

Advanced International Studies 
Programs 

The FIC contributes to advanced studies in the health 
sciences through three interrelated programs: the 
International Issues Study-Program, International Confer- 
ences Program, and Scholar-in-Residence Program. These 
have the same broad goal: to bring the knowledge and 
ideas of experts to bear on the identification of 
health-related issues of international importance and 
concern, and to develop strategies that will have a 
worldwide impact on prevention and control of dis- 
eases in the United States as well as abroad. They 
provide opportunities for the development of plans for 
activities that will have an impact on international 
health, for exchange of knowledge and ideas, and for 
intellectual stimulation. 

International Issues Study-Program 

The International Issues Study-Program is a new 
program under development. It addresses problems 
concerning international aspects of biomedical and 
behavioral research, research manpower training, and 
the transfer of research results to bring new knowledge 
to bear where it will benefit international health. 

The following studies and activities were in various 
stages of planning in 1981: 

^International Symposium on Measles Immunization: An 
organizing committee was established which involved 
FIC and representatives from WHO; PAHO; the 
Centers for Disease Control (CDC); NICHD; NIAID; 
Bureau of Biologies; FDA; US AID; Institute of Medicine; 
and the American Public Health Association. An 
international svmposium will be held March 16-19, 
1982, at which the following topics will be discussed: 
the socioeconomic and medical impact of measles 



11 



throughout the world; current immunizing materials 
and programs; further research; and the programs and 
efforts needed to bring measles to the point at which 
eradication will be possible. 

•International Symposium on Control of Poliomyelitis and 
the Feasibility of Eradication: An organizing committee 
has been established with members from FIC; WHO; 
PAHO; Institute of Medicine; CDC; Bureau of Biologies, 
FDA; USAID; MAID; NICHD; NINCDS; and the 
University of Washington School of Public Health. The 
planned symposium will look at the impact of 
poliomyelitis through the world, and a consensus will 
be reached on measures to be taken for the eradication 
of poliomyelitis. The resulting publication will provide 
guidance for international health organizations and the 
national health services of all countries. 
•The Use and Abuse of Antibiotics: Current procedures in 
many countries for the distribution and use of antibio- 
tics are giving rise to a growing number of strains of 
disease organisms resistant to the lethal effects of 
antibiotics, thus reducing the effectiveness of classical 
treatments for a number of important diseases. Pre- 
liminary discussions occurred with representatives of 
the PAHO, the Institute of Medicine, and several of the 
mission-related Institutes at NIH about the develop- 
ment of an international project concerned with this 
subject. 

•Task Force on Standardization of Nomenclature and 
Diagnostic Procedures for Digestive Diseases: The NIH 
Coordinating Committee on Digestive Diseases re- 
quested FIC to undertake this project after considerable 
discussion as to its nature and importance. A Digestive 
Diseases Task Force Steering Committee was set up by 
FIC to plan the project, and the planning process is 
likely to continue through FY 1983. 

A study is identified as an international issue if it 
meets the following criteria: 
•Involves more than one country. 
•Requires cooperation among various countries to 
solve the problems. 

•Benefits the U.S. if the problem is solved. 
•Is appropriate to the NIH mission. 
•Has a feasible solution in light of the present state of 
knowledge and appropriate resources. 

The operational strategy of the International Issues 
Study-Program is to: identify international health issues 
that should receive the attention of the categorical 
Institutes as well as the FIC; bring together experts to 
formulate questions to be answered in identifying and 
selecting alternative programs or activities; and bring 
together experts to develop an operational plan for 
actions by the FIC, appropriate NIH categorical Insti- 
tutes, or other Federal agencies. 

Various support mechanisms are to be used which 
are characterized by sponsorship by a number of 
national and international organizations, including 
WHO and PAHO, and participation by scientists and 
authorities from a number of countries. 

The Study-Programs, administered by FIC staff, 
draw upon the expertise of the Scholars-in-Residence 
Program, scientists within the various categorical 



Institutes of the NIH, as well as outside groups and 
consultants to formulate recommendations and plans. 

International Conferences Program 

The International Conferences Program fosters ad- 
vanced international studies in the health sciences 
through meetings and conferences that provide oppor- 
tunities for biomedical and behavioral scientists from 
various parts of the world to share their knowledge, 
ideas, and concerns about international health, and to 
evaluate ongoing research. 

In 1981, five intramural conferences were orga- 
nized by Scholars-in-Residence and NIH scientists 
working together. These were: 

•"Symposium on Current Topics in Biostatistics and 
Epidemiology." 

• "International Task Force on Animal Models 
Appropriate for Research on Diabetes." 
•"International Symposium on the Contributions of 
Chemical Biology to the Biomedical Sciences." 
•"International Symposium on Acclimatization, 
Adaptation, and Tolerance to High Altitudes." 
•"Conference on Cytochemical Methods in Neuroanat- 
omy." 

The FIC also supports international aspects of 
extramural conferences that have been submitted to 
NIH as conference grant applications. These applica- 
tions are reviewed by a peer group for scientific merit, 
and by an FIC panel for international importance in 
evaluation of funding. Of the 68 extramural conferences 
partially sponsored by FIC, 23 were held overseas, and 
the rest were in the U.S., Canada, or Mexico. They 
covered the broad field of biomedical and behavioral 
research, including fundamental research, clinical stu- 
dies, and developmental research. 

Several conferences are of particular note: 
•2982 International Symposium on Viral Hepatitis, March 
20- April 2, 1981, New York, New York: Perhaps no other 
scientific area has advanced as rapidly as that of viral 
hepatitis. Within a period of 15 years, the detection of a 
then-unidentified antigen (Australian antigen) has led 
to landmark discoveries. Major highlights of this 
meeting were the results of immunization research. A 
highly effective hepatitis B vaccine has been developed; 
a prototype hepatitis A vaccine is nearly ready for 
clinical trials; and a hyperimmune hepatitis B globulin, 
which is given to infants usually within an hour of birth, 
proved to be efficacious even when the mothers were 
carriers of hepatitis. Research presented at the sympo- 
sium indicated that, overall, the HBV vaccine was 
extremely safe, highly immunogenic, and almost 
perfectly active among those who responded with the 
development of antisurface antibody. 

•Tenth International Narcotic Research Conference: Ad- 
vances in Endogenous and Exogenous Opioids, July 26-30, 
1981, Tokyo, Japan: The Tenth International Narcotic 
Research Conference in Japan was considered the most 
important and definitive annual meeting dealing with 
the frontiers of the state-of-the-art in research on opiate 
receptors and opioid peptides. This international 
conference received a funding contribution from 
National Institute on Drug Abuse (NIDA), NIMH, NCI, 



12 



and FIC and was attended by scientists from 20 
countries. 

•The Third International Conferences on Environmental 
Mutagens, September 21-27, 1981, Tokyo, Japan: The FIC in 
conjunction with NCI, NIEHS, and the U.S. Environ- 
mental Protection Agency (EPA) provided partial 
financial support for the Third International Conference 
on Environmental Mutagens, which attracted partici- 
pants from 33 nations. 

An understanding of the extent to which results 
from in vitro tests can be extrapolated to the human 
situation remains rudimentary. The research trend is 
toward direct assays for mutagenic effects in somatic 
and germ cells of laboratory mammals and humans. 
However, it was noted that a fuller understanding of 
the effects of chemical mutagens on the somatic and 
germ cells of laboratory animals is essential in order to 
predict with some confidence the risk that exposure to a 
given chemical will represent. 

•Genetic Variation Among Influenza Viruses, March 8-13, 
1981, Salt Lake City , Utah: To foster better understanding 
of the mechanism of genetic variation among the 
influenza viruses and how to cope with it, this major 
international meeting was sponsored in part by NIAID, 
BOB/FDA, FIC, and CDC. Reports at the conference 
concerned attempts made, using recombinant DNA 
technology and rapid DNA sequencing techniques, to 
elucidate the variation at the levels of the nucleotide 
sequence of individual genes, and how such a sequence 
variation is translated into antigenic variation by 
changes in the amino acid sequence of viral proteins. 

•International Conference on the Biology of the Interferon 
System, April 21-24, 1981, Rotterdam, The Netherlands: A 
critical impediment to the study and therapeutic use of 
the interferons has been a shortage of this rather 
expensive material. A demand for more and better 
purified interferon preparations has motivated a num- 
ber of research groups to address themselves to the 
problem of interferon production. The technologies of 
large-scale tissue culture and of recombinant DNA are 
being successfully applied, and a large body of data, in 
need of critical review and discussion, has accumulated 
on the international science scene. NCI, NIAID, and 
FIC provided sponsorships and partial funding support 
for the conference that addressed this issue. 

No firm conclusions can as yet be drawn regarding 
true percentages of response under any given regimen 
of treatment, or potential benefit to patients, or relative 
efficacy of interferon treatment when compared with 
other therapies. The need for substantial antiviral and 
antitumor trials in man clearly emerged from the clinical 
work reported at the international conference. Ad- 
vances in several areas are progressively reducing the 
high cost of interferon so that the cost of its use in 
treatment, even against cancer, may very soon compare 
favorably with the cost of some other therapies. 

•Recent Developments in the Genetics of Insect Disease 
Vectors, April 20-24, 1981 , Lake Como, Italy: Five of the six 
major diseases of mankind (i.e., malaria, filariasis, 
schistosomiasis, trypanosomiasis, and leishmaniasis) 
are vector-borne; only leprosy is not. The World Health 



Organization has estimated that these great parasitic 
diseases affect more humans directly (via disease 
processes) or indirectly (via economic processes) than 
any other form of disease. The developing countries of 
the tropical world are principally affected. Malaria is the 
most important disease in at least 70 countries, with 
over 400 million cases reported annually. In the last 5 
years there has been a general worldwide increase of up 
to threefold in malaria cases. 

To address this problem, and its possible solution, 
the FIC, NIAID, and the U.S. Department of Agricul- 
ture provided support and partial funding for an 
international meeting of leading geneticists on the 
insect vectors that transmit these diseases. The confer- 
ence participants represented countries and research 
from almost all countries of the world. 

Scholars-in-Residence Program 

The purpose of the Scholars-in-Residence Program is to 
enable established scientists and scholars interested in 
international health to exchange information and ideas 
through preparation of a book, monograph, or other 
report; arrange meetings to foster interaction with other 
scholars and scientists; and collaborate in research in an 
environment conducive to innovative approaches to 
international health issues. 

Scholars-in-Residence may be nominated by NIH 
scientists or former Fogarty scholars. Nominees are 
reviewed by an NIH panel of senior intramural 
scientists. Approved nominees are invited by the FIC as 
openings in the program become available. 

Since 1970, 97 scholars from 21 countries have 
participated in the program. During FY 1981, 22 
scholars participated for varying periods of time as 
shown below. 

Of the 22, 8 were U.S. citizens, the others came 
from Sweden (2), U.K. (1), Israel (5), France (2), China 
(1), Japan (1), and Taiwan (1). These numbers represent 
the continued expansion of the program begun in FY 
1979 and FY 1980 aimed at achieving a steady state of 10 
Scholars-in-Residence at any given time. The average 
stay was 5 months, but the majority (11) of the Scholars 
were in residence for 3 months. Six Scholars stayed for 7 
months or longer. Nine of the 22 were returnees; the 
rest were new to the program. 

All of the Scholars have participated regularly in 
the intramural research seminars at the Stone House 
conducted by the Senior Science Advisor to the Office of 
the Director, NIH. They also met regularly throughout 
the year for a brown-bag lunch journal club at which 
they discussed their work and shared their perceptions 
of contemporary research programs. 

Three major conferences in the Advanced Studv 
Program organized by Scholars-in-Residence took place 
during 1981. The first of these, organized by Professor 
Carlos Monge, Cayetano Heredia Universidad, Lima, 
Peru, was a "Symposium on Acclimatization, Adapta- 
tion, and Tolerance to High Altitude." The second, 
organized by Drs. Sanford Palay and Victoria Chan- 
Palay, Harvard Medical School, Boston, was devoted to 
"Cytochemical Methods in Neuroanatomy." The third 
meeting was a workshop on "Affinity and Photoaffinity 



13 



Scholars-in-Residence During FY 1981 1 



Dr. Herman Kalckar 
Professor of Chemistry 
Boston University, U.S.A. 

Dr. Rolf Luft 
Professor of Medicine 
Karolinska Instituted Sweden 

Dr. David Shemin 

Chairman 

Dept. of Biochemistry & Molecular Biology 

Northwestern University, U.S.A. 

Dr. Bracha Ramot 

Professor of Medicine and Head, Department of 

Hematology 
Chaim Sheba Medical Center 
Tel Aviv University, Israel 

Dr. Howard Schachman 
Professor of Molecular Biology 
University of California, U.S.A. 

Dr. Jerard Hurwitz 
Professor and Chairman 
Developmental Biology and Cancer 
Albert Einstein College of Medicine, U.S.A. 

Dr. Hsiang-Tung Chang 

Director 

Shanghai Brain Research Institute 

Academy of Sciences, People's Republic of China 

Dr. Marianne Grunberg-Manago 

Director of Research, C.N.R.S. 

Head, Department of Biochemistry 

Institut de Biologie Physico-Chimique, France 

Dr. Sanford Palay 
Professor of Anatomy 
Harvard Medical School, U.S.A. 

Dr. James Metcalfe 
Professor of Biochemistry 
University of Cambridge, U.K. 

Dr. Carlos Monge 

Rector 

Cayetano Heredia Universidad, Peru 



Dr. Sidney Bernhard 
Professor of Molecular Biology 
Univesity of Oregon, U.S.A. 

Dr. Franklin Bunn 

Director, Hematology Division 

Peter Bent Brigham Hospital, U.S.A. 

Dr. Susan Lowey 

Professor of Biochemistry 

Rosentiel Basic Medical Science Research Center 

Brandeis University, U.S.A. 

Dr. Nathan Sharon 

Head, Department of Biophysics 

The Weizmann Institute of Science, Israel 

Dr. Meier Wilchek 

Professor of Biophysics 

The Weizmann Institute of Science, Israel 

Dr. Haruaki Yajima 

Professor of Pharmaceutical Chemistry 
Faculty of Pharmaceutical Sciences 
Kyoto University, Japan 

Dr. Giorgio Bernardi 

Director of Research 

Institute of Molecular Biology 

National Center for Scientific Research, France 

Dr. Hans Lindner 

Chairman 

Department of Hormone Research 

The Weizmann Institute of Science, Israel 

Dr. Tomas Hokfelt 

Professor, Department of Histology 

Karolinska Institutet, Sweden 

Dr. Shmuel Shaltiel 

Dean, Feinberg Graduate School 

The Weizmann Institute of Science, Israel 

Dr. Chen- Yuan Lee 

Dean, College of Medicine 

National Taiwan University, Taiwan, China 



1 Funds may have been obligated in FY 1981 or in previous fiscal years 

Labeling," organized by Dr. Meier Wilchek, Weizmann 
Institute, Israel, in collaboration with the NIH Peptide 
Discussion Group. This meeting, involving mostly NIH 
staff, considered the latest techniques for identification 
and characterization of biologically active molecules in 
tissues and in the circulation. It has wide implications 
for application to the study of cell function, using 
monoclonal antibodies, and to the elucidation of 
immunologic defense mechanisms against disease- 
causing organisms. 



International Research and Awards 
Program 

The Fogarty International Center has always viewed as 
one of its most important functions the sponsorship of 
opportunities for U.S. scientists to work abroad and for 
foreign scientists to work in the United States for limited 
periods of time in direct collaboration. Such experiences 
broaden horizons, stimulate innovation, permit cost- 
effective sharing of resources, and upgrade scientific 
skills. Through cooperative arrangements with other 
countries and international organizations, the Center 
administers fellowship and exchange programs involv- 



14 



ing both U.S. and foreign scientists at the various levels 
of postgraduate experience. 

There are four fellowship programs which are 
supported fully or partially by the FIC. These are the: 
International Research Fellowships; Senior Internation- 
al Fellowships; WHO/NIAID International Tropical 
Diseases Fellowships; and WHO/NINCDS/FIC Interna- 
tional Neurosciences Fellowships. There are three other 
fellowship programs which are administered by the FIC 
but are supported by the Governments of France, 
Switzerland, and Sweden. These programs are the: 
French National Institute of Health (INSERM) Fel- 
lowships; Swiss National Science Foundation Fel- 
lowships; and Swedish Medical Research Council 
Fellowships. 

International Research Fellowships 

The International Research Fellowship Program (IRFP) 
provides opportunities for postdoctoral biomedical or 
behavioral scientists who are in the formative stages of 
their research careers to extend their research experi- 
ences in a laboratory in the United States. These 
fellowships serve to forge relationships between dis- 
tinguished scientists in the United States and qualified 
scientists in other countries in order to resolve health- 
related problems of mutual interest. 

During FY 1981, there were 44 participating 
countries with National Nominating Committees. Thir- 
ty-seven National Nominating Committees selected 129 
applicants for the program. Of this number, 96 (78.74 
percent) were funded. Recipient countries of fellowship 
awards are shown below. 

1981 International Research Fellowship 
Awards by Country of Applicant 



Americas 


14 


Taiwan 


3 


Argentina 


1 


Thailand 


1 


Brazil 


3 






Canada 


3 


Europe 


52 


Chile 


2 


Austria 


— 


Colombia 


- 


Belgium 


4 


Mexico 


4 


Denmark 


1 


Peru 


1 


Finland 


6 


Uruguay 





France 


6 


Venezuela 


- 


Germany, Fed. Rep. 


1 






Greece 


1 


Africa 


7 


Iceland 


3 


Egypt 


1 


Ireland 


3 


Nigeria 


4 


Italy 


3 


South Africa 


- 


Netherlands 


2 


Sudan 


1 


Norway 


5 


Tanzania 


1 


Poland 


2 


Zimbabwe 


— 


Spain 


5 






Sweden 


6 


Asia & Far East 


20 


Switzerland 


3 


Australia 


4 


United Kingdom 


2 


Hong Kong 


- 


Yugoslavia 


1 


India 


4 






Japan 


6 


Middle East 


3 


Korea 


1 


Israel 


3 


New Zealand 


1 


Lebanon 





Singapore 


- 







During the past year the following program 
changes were made: 

•A tentative decision was made that all fellowships 
would be awarded for only 1 year. This will allow more 
scientists to take advantage of the program. However, 
with good justification, fellowships may be extended 
for up to 6 months. 

•In FY 1981, three National Nominating Committees 
were activated. These were in Romania, Venezuela, 
and Zimbabwe. The People's Republic of China plans to 
establish a committee. 

•The receipt date for application was changed from 
December 1 to September 1. 

Some FY 1981 IFRP projects of particular interest 
are: 

•Mapping rat brain for antihistamine and B-adrenergic 
receptors using a new method of studying the bindings 
of ligands to neurotransmitters and drug receptors in 
the brain. 

•Studying optimal methods for storing platelet concen- 
trates by looking at platelet senescence, types of cells in 
platelet concentrates that survive the procedures for 
separating platelets from whole blood, and protection 
during the isolation procedure. 

•Studying molecular basis of liver injury specifically as 
it relates to derangement in albumin synthesis. 

The International Tropical Diseases Research 
Fellowships 

The FIC in cooperation with the National Institute of 
Allergy and Infectious Diseases and with the United 
Nations Development Program (UNDP)AVorld Bank/ 
WHO Special Program for Research and Training in 
Tropical Diseases has established a program for a 
limited number of postdoctoral fellowships for training 
in tropical diseases. Candidates for these fellowships 
are from countries in which these diseases are endemic: 
malaria, schistosomiasis, leishmaniasis, trypanoso- 
miasis, filariasis, and leprosy. No awards were made in 
FY 1981. 

International Neurosciences Fellowships 

The International Neurosciences Fellowships Program 
was established in 1977 in cooperation with the 
National Institute of Neurological and Communicative 
Disorders and Stroke (NINCDS) and the World Health 
Organization. It is administered by the FIC with funds 
provided by NINCDS. There were two active fellows 
during FY 1980, but no new awards were made. 

Senior International Fellowships 

The Senior International Fellowship Program (SIFP) 
provides opportunities for established biomedical or 
behavioral researchers to do collaborative research in a 
foreign institution. The Senior International Fellowship 
serves to enhance the exchange of ideas and informa- 
tion about the latest advances in specific areas of 
medicine, both basic and clinical. It also leads to 
improvement in the research, education, and clinical 
potential of the U.S. nominating institution, which 
profits from the fellows' experience abroad. 

During FY 1981, U.S. institutions nominated 114 
scientists for the fellowship program. Of this number, 



15 



27 percent were funded. The table below lists the host 
countries which received SIFP fellows. 

1981 Senior International Fellowship 
Awards by Country of Destination 



Americas 


1 


Middle East 


1 


Peru 


1 


Israel 


1 


Africa 





Europe 


27 






United Kingdom 


16 


Asia & Far East 


2 


France 


3 


Japan 


1 


Switzerland 


3 


Australia 


1 


Sweden 


1 






Belgium 


1 






Germany, Fed. Rep. 


3 



The SIFP is marked by mutually beneficial col- 
laboration. Some examples are: 

•Development of a method to quantitatively analyze 
Doppler ultrasound spectra patterns to help assess 
more accurately vessel wall changes, flow disturbances, 
and flow lesions in the carotid system. This technique is 
especially useful in the retina, where an invasive 
technique poses a great risk to the patient. 
•Exchange of methods for studying organization of 
genes and a DNA hybridization technique for knowl- 
edge on biology of trypanosomes. This work may be 
applicable to influenza viruses and make possible the 
development of an effective vaccine. 

Special Emphasis Senior International Fellowship 
Programs 

These programs have the same purpose and eligibility 
criteria as the Senior International Fellowship Program. 
Since these programs are administered by the FIC in 
cooperation with the National Institute on Aging, the 
National Institute of Arthritis, Diabetes, and Digestive 
and Kidney Diseases, and the National Institute of 
Neurological and Communicative Disorders and 
Stroke, the emphasis is on aging, arthritis, diabetes, 
and epilepsy. For 1981, one award was made by 
NIADDK for work in arthritis in Australia. 

Foreign Government Fellowships 

Currently three countries provide fellowships for U.S. 
scientists to conduct research abroad: Sweden, Switzer- 
land, and France. These are sponsored, respectively, by 
the Swedish Medical Research Council, the National 
Science Foundation of Switzerland, and the French 
National Institute of Health and Medical Research 
(INSERM). The FIC publicizes the program, advises 
prospective applicants about the program, reviews the 
applications for document compliance, monitors the 
review proceedings, and forwards the applications and 
summary statements to the appropriate awarding 
agency. The foreign country agency makes its own 
funding decision, independent of FIC. In FY 1981, 
Sweden awarded three fellowships, and Switzerland 
awarded four. The INSERM program is in its initial 
phase and made no awards. 



Individual Health Scientist Exhange Programs 

The Fogarty International Center, on behalf of the 
Public Health Service, administers Individual Health 
Scientist Exchange Programs with France, Poland, 
Romania, U.S.S.R., and Yugoslavia. These programs 
are components of broader intergovernmental bilateral 
agreements for cooperation in science and technology, 
including health, and serve the broad range of health 
interests of the PHS and the respective foreign minis- 
tries of health. They provide mutual opportunities for 
health professionals to become personally familiar with 
various aspects of public health and biomedical re- 
search activities of the participating host country. By 
providing support for short- and long-term exchanges, 
the programs encourage and facilitate direct collabora- 
tion and communication between health and biomedi- 
cal communities of the United States and the participat- 
ing countries. Through the promotion of person-to- 
person relationships, the basic goal of the exchange 
programs is to expand and disseminate scientific 
knowledge and to foster scientific growth. 

•Under these programs, during FY 1981, one American 
scientist visited Poland to study that country's health 
policies, planning, and programs relevant to mental 
health aspects of primary health care, as part of an 
overall comparative study. Six Polish scientists visited 
the United States for training in the fields of vascular 
and abdominal surgery, surgical treatment of ischemic 
heart disease, thrombosis research, electron micros- 
copy of the haemic cells, hearing impairments, and 
kidney transplants. 

•Seven American scientists visited Romania to conduct 
a joint workshop on immunology, and one Romanian 
scientist visited the NIH to discuss future collaboration 
in cancer research. 

•One American scientist visited the Soviet Union to 
continue his work on the preparation of a biography on 
Nikolai A. Semashko, the architect and founder of the 
Soviet health care system; and 10 Soviet scientists, 
interested in such diverse areas as organ and tissue 
transplants, pain management in dentistry, lysosomes, 
hearing aids, coronary surgery, and viral infections, 
visited a number of research institutions in the United 
States. 

•Four scientists from Yugoslavia received training in 
radiology, pediatrics, and orthopedic surgery. 

Under an agreement between the NIH and the 
French National Center for Scientific Research (Centre 
National de Recherche Scientifique), the two organiza- 
tions share in the support of U.S. scientists selected to 
work at U.S. laboratories for periods of generally 6-12 
months. The type of activity undertaken with a host 
laboratory may include the conduct of basic or clinical 
research, familiarization with or utilization of special 
techniques and equipment not otherwise available, 
and/or related cooperative efforts. Scientists supported 
under this program are expected to achieve specific and 
substantive goals. Seventy-five person-months of work 
are supported annually by each side. During FY 1981, 10 
U.S. scientists worked in French laboratories, and 12 
French scientists worked in U.S. laboratories. 



16 



NIH Foreign Scientists Assistance 
Programs 

NIH Visiting Program 

Foreign scientists have the opportunity to work with 
NIH scientists in their laboratories under the NIH 
Visiting Program. FIC provides administrative services 
to support these scientific exchanges on behalf of the 
various Institutes. The fellowships provided under this 
program are funded by the respective Institutes. 
Administrative support is also provided by FIC for three 
non-NIH organizations: the Bureau of Biologies of the 
Food and Drug Administration, the National Institute 
of Mental Health, and the National Institute on Alcohol 
Abuse and Alcoholism of the Mental Health Adminis- 
tration. Program participants must be invited by a 
senior intramural investigator (who will sponsor the 
visitor's research), and must hold a doctoral degree or 
the equivalent and have postdoctoral research experi- 
ence. 

The three types of visiting program participants 
are: 

•Visiting Fellows, who have not had more than 3 years' 
postdoctoral research experience, must be foreign 
nationals, and receive a 1-year award which is renew- 
able for 2 years. 

•Visiting Associates, who have 3 to 6 years' postdoctor- 
al research experience. 

•Visiting Scientists, who have more than 6 years' 
postdoctoral research experience. 

Visiting Associates and Scientists are appointed as 
temporary NIH employees for 12-13 months; their 
appointments may be renewed for up to 3 additional 
years. Foreign appointees are subject to visa restric- 
tions. The appointment of a U.S. citizen may be 
requested only on limited occasions when a Civil 
Service, Staff or Senior Staff Fellow, or Commissioned 
Corps appointment is not feasible and subsequent 
conversion to a permanent appointment is not antici- 
pated. 

Distribution of Visiting Program 
Participants from Top 10 Countries 
FY 1981 



Foreign Countries 


No. of Participants 


U.S. $ 


Japan 


183 


$2,552,000 


India 


126 


2,000,000 


Israel 


69 


1,185,000 


United Kingdom 


73 


1,159,000 


Italy 


74 


1,039,000 


Canada 


35 


529,000 


Sweden 


26 


526,000 


Australia 


28 


319,000 


Germany 


18 


300,000 


Switzerland 


19 


299,000 



The total Visiting Program participation for all 
Institutes and NIMH, NIAAA, and BOB in FY 1981 was 
1,059 individuals, including 16 U.S. citizens; 155 
resident aliens, refugees, and stateless persons; and 888 
foreign scientists from 50 countries. There were 707 



Visiting Fellows, 192 Visiting Associates, and 157 
Visiting Scientists at a cost of $15.8 million of intramural 
research funds. This is an increase of 66 individuals over 
the FY 1980 total of 993 and an increase in total funding 
of $2.3 million. The distribution of countries with the 
greatest activity is shown below. 

NIH Foreign Guest Researchers Program 

NIH also makes research and study facilities available to 
qualified scientists who are supported by home institu- 
tions and foreign and domestic foundations. NIH has 
invited Guest Researchers to use intramural facilities 
since the 1930' s; FIC has been responsible for foreign 
participants since 1968. 

In addition to administering the NIH Visiting 
Program, the Foreign Scientists Assistance Office 
(FSAO) provides a limited advisory service to other 
foreign scientists at NIH, particularly in immigration 
matters. In FY 1981, the FSAO assisted 457 additional 
foreign scientists. Seventy-seven percent were Guest 
Researchers funded by sources within their home 
countries; 9.5 percent were experts funded by the 
Institutes; and 13 percent were scientists on bilateral 
agreements, FIC International Research Fellows located 
at NIH, and Fogarty Scholars. These scientists repre- 
sented the following geographic areas: 

Guest Special All 

Researchers Experts Others 

Europe 187 24 36 

Africa 8 2 

Middle East 15 2 6 

Asia and the Far East 101 2 

Latin America 24 4 3 

North America (Canada) 20 (Canada) 1 (Canada, 6 

5 U.S.) 

Special Foreign Currency and Joint 
Funds Programs 

The Special Foreign Currency (SFCP) and the Joint 
Funds Programs are unique resources which enable 
NIH to engage in international collaborative research 
and information exchange with biomedical researchers 
of selected countries for the purpose of investigating 
health problems of mutual interest and importance. The 
collaborative character of the NIH program requires 
that a scientist from an intramural NIH program or from 
a U.S. academic institution participate in a research 
project. The participating scientists from both countries 
select the problem and develop the experimental 
design. The proposal is submitted to NIH through a 
coordinating agency in the foreign country for assess- 
ment of technical merit by the NIH peer review system. 

The SFCP is funded in those countries with 
currencies designated annually by the Department of 
Treasury and Office of Management and Budget as 
excess to the needs of the United States during the 
subsequent 2 years. The excess currency countries 
during FY 1981 were Burma, Guinea, India, and 
Pakistan. 

When it has become apparent that funds would be 
depleted and a country would be removed by the 
Treasury Department from the excess currency list, the 



17 



State Department has negotiated various types of 
agreements and joint funds, to which each country has 
contributed equally. To maintain the scientific contacts 
established under the SFCP, these agreements provide 
for the use of the residues of U.S. -owned local 
currencies to establish scientist-to-scientist exchange 
programs. The agreements also endorse the establish- 
ment of institute-to-institute agreements between U.S. 
academic and research institutions for foreign institu- 
tions, which must be funded by the institutions 
themselves. Countries which have established agree- 
ments or joint funds are Poland and Yugoslavia. 
Activity in the SFCP and Joint Funds Program for FY 
1981 is shown below. 

One project being funded under the SFCP is a 
genetics unit consisting of laboratory clinics and a 
counseling center in Cairo, Egypt, where there is a high 
prevalence of congenital and metabolic abnormalities 
and chromosomal defects resulting from traditional 
marriage practices. This laboratory was the first to 
describe certain chromosomal defects subsequently 
confirmed elsewhere. It has provided the basis for 
advocating measures to reduce the potential for birth 
defects in the population as well as in individual 
families. It has also provided U.S. scientists with a 
source of clinical material such as that for the study of 
xeroderma pigmentosa, a rare genetic skin disorder in 
which mental retardation and neurological disturb- 
ances occur and in which extreme sensitivity to sunlight 
produces loss of skin pigment, scarring, and severe skin 
cancers. Studies of individual cells reveal that there are 
gene products missing which prevent the ultraviolet 
damage of DNA. 

Number of Applications 
Country Submitted Funded Continuations 

SFCP Funds 14 10 1 

Egypt 8 4 1 

Joint Funds 
Program 

Poland 3* 

Yugoslavia 14 1** 



awaiting review 

(5) appropriation and deposits 



International Coordination and Liaison 
Program 

The International Coordination and Liaison Program 
(ICLP) serves the key role of coordinating NIH 
international relationships to facilitate the interaction of 
scientists and to assist in the exchange of scientific 
information. It has a liaison responsibility for facilitating 
communications between NIH and other international 
offices or agencies. It provides policy guidance, coor- 
dination, and general oversight for the participation pf 
NIH with other U.S. agencies in bilateral cooperative 
agreements between the U.S. Government and other 
countries. 

Bilateral Agreements 

The United States is making major contributions toward 



the resolution of a broad spectrum of international 
health problems through its domestic research and 
related efforts, its cooperative health relationships with 
other countries, and its participation in the programs 
and activities of international organizations, notably the 
World Health Organization (WHO) and the Pan 
American Health Organization (PAHO). Formal inter- 
governmental agreements may take a variety of forms, 
ranging from those of broad scope for educational, 
cultural, and scientific exchange to more specific ones in 
science and technology or the health fields. In some 
instances, a health agreement may be subsidiary to a 
broader agreement in science and technology. Less 
formal technical-level agreements may also exist direct- 
ly between counterpart institutes for a particular 
purpose. 

The bilateral agreements are formal agreements 
between the Governments of the United States and 
other countries for cooperative activities; however, 
much international cooperation in biomedical research 
occurs without formal mechanisms. The formal agree- 
ments form a basis for cooperation in particular 
situations and circumstances, such as utilizing special 
resources or surmounting constraints of different social 
and political systems. 

The International Coordination and Liaison Prog- 
ram coordinates NIH participation in all bilateral 
agreements which involve NIH components and scien- 
tists. There are three types of bilateral agreements: 
•Agreements made at the government-to-government 
level which promote broad science and technology 
objectives. 

•Agreements between department-level agencies 
which may have general preventive health or health 
maintenance objectives, and which may be concerned 
with specific disease issues. 

•Agreements between NIH and a foreign counterpart 
in which specific components of NIH are identified as 
participating in particular disease or biomedical re- 
search areas. 

During the last decade, international health re- 
search and related activities being conducted by 
DHHS/PHS, and particularly by the NIH, have increas- 
ingly been planned as collaborative efforts and have 
been instituted through special bilateral arrangements. 
Since the first formal program was signed with Japan in 
1965, more than 20 bilateral health agreements have 
been signed directly between DHHS officials and 
officials of foreign ministries of health. 

Highlights of Bilateral Agreements in FY 1981 

New bilateral relationships continue to emerge: 
•In FY 1981, a new health agreement, in which the NIH 
will play an important role, was signed with Kuwait. 
•In followup to the opening of formal science and 
technology relationships in 1980, the NIH initiated 
consultation with the Zimbabwe Ministry of Health in 
1981 regarding potential cooperative activities in biome- 
dical research fields. 

•The NIH and officials from the Israeli Ministry of 
Health held consultations to implement the U.S. -Israel 
Health Agreement. U.S. areas of interest for continued 
or new activities have been identified and are currently 



18 



under review by Israel for its reaction and counterpro- 
posal. 

•Formal implementation of the health agreements with 
Nigeria and Venezuela are expected in 1982, following 
discussions that have taken place during 1981. The 
Nigerian Agreement was signed in September 1981; the 
Venezuelan Agreement, in January 1980. 

At present there are 41 agreements which involve 
NIH with 26 countries. Major agreements are with 
China, U.S.S.R., other Eastern European countries, 
Japan, Egypt, Israel, India, and Nigeria. The NIH 
participates with the following countries in broad 
agreements covering science and technology coopera- 
tion for which the Department of State or the National 
Science Foundation serves as the executive agency: 
Egypt, France, India, Israel, Italy, Japan, Nigeria, 
Pakistan, Poland, Romania, Spain, U.S.S.R., Vene- 
zuela, and Yugoslavia. The NIH occasionally partici- 
pates in agreements with Argentina, Australia, Brazil, 
Greece, Kenya, Mexico, Senegal, and Zimbabwe. 
Although the FIC has a role in the administration of 
bilateral agreements, the scientific content of the 
projects supported in foreign countries is selected by 
the collaborating scientists at the NIH in cooperation 
with the foreign scientists. 

Significant events during FY 1981 were: 
•The Second Joint Health Committee Meeting was held in 
Beijing in November 1980 with the People's Republic of 
China. Agreement was reached upon programs for 
hepatitis B vaccine development in China; major 
epidemiologic study of cardiovascular disease in 
selected populations in China; a descriptive study of 
health care and health services in Shanghai city and a 
reciprocal study by the Chinese in an analogous county 
in the U.S. The meeting was preceded by a scientific 
symposium on epidemiology. 

•In October 1980, a U.S. -Federal Republic of Germany 
(U.S.-FRG) cancer working group convened in Bethesda, 
Maryland, to review a series of proposals for coopera- 
tion. As a result of these discussions, the working group 
developed a joint protocol for a Drug Development and 
Testing Program for Cancer Therapy. This protocol, 
which provides for a variety of cooperative and 
exchange activities, was endorsed in a Memorandum of 
Understanding signed by representatives of the NCI 
and the FRG Ministry for Research and Technology 
(MORT) in September 1981. In April 1981, a delegation 
of U.S. cardiovascular disease specialists participated in 
a joint workshop on Multiple Risk Factor Intervention 
Trials in the FRG and reached agreement on several 
cooperative activities to be carried out over the next 2 
years. In the first of these activities, a U.S.-FRG working 
meeting was held in Bethesda during September- 
October 1981, for the purpose of discussing cooperative 
activities with the German National Health Survey on 
cardiovascular disease. 

•In followup to the U.S. -Israel Health Agreement initiated 
in 1980, NIH and Israeli Ministry of Health officials 
consulted during 1981 on the development of a 
cooperative program to be implemented in biomedical 
research under the Agreement. U.S. areas of interest for 
continued or new activities have been identified and are 



currently under review by Israel. It is anticipated that 
formal agreement will be reached in mid-1982. 

•In July 1981, the Seventeenth Meeting of the Joint 
Committee of the U.S. -japan Cooperative Medical Science 
Program (U.S.-JCMSP) met at the NIH. The committee 
discussed the reports of scientific progress from the 
eight joint panels on Cholera, Environmental 
Mutagenesis and Carcinogenesis, Hepatitis, Leprosy, 
Malnutrition, Parasitic Diseases, Tuberculosis, and 
Viral Diseases. The Committee expressed its continued 
satisfaction with the research progress, program guide- 
lines, future plans, and priorities of each of these 
panels. The third 5-year report (1975-80) of the U.S.- 
JCMSP became available in September 1980. 
•Following a restructuring of the program under the 
U.S. -Japan Agreement for Cancer Research, emphasis was 
placed on cancer etiology, biology, diagnosis and 
treatment, and interdisciplinary programs. A confer- 
ence was held on the etiology and epidemiology of 
stomach and colon cancer. In the treatment area, 
cooperation was extended to the development of new 
anticancer drugs and to cooperative clinical trials in 
treatment of gastric cancer. There was continuing 
interaction on immunology and immunotherapy for 
cancer. 

•Under the Agreement between the U.S. and Japan on 
Cooperation in Research and Development in Science and 
Technology (the so-called Non-Energy Agreement), 
cooperation is presently underway in seven areas: the 
National Toxicologv Program, Alcoholism, Immuniza- 
tion, Laboratory Animal Science, Recombinant DNA, 
Development of Antivirals, and Cardiovascular Disease 
(Hypertension). The first joint meeting in the coopera- 
tive area for recombinant DNA took place February 4-5, 
1981, in Honolulu, Hawaii. The participants exchanged 
information on guidelines, host-vector systems, and 
risk assessment. 

•In May 1981, a Memorandum of Agreement between 
DHHS and the Ministry of Health of Kuwait was signed to 
establish a formal mechanism through which public 
health technical assistance could be obtained on a 
reimbursable basis. No specific areas of interest have 
been identified as yet. 

•Under the U.S. -Nigeria cooperative agreement in health, 
the NIH will have the lead role in the subcommittee 
program area of biomedical research (multiple Insti- 
tutes). NIEHS and NIOSH will share responsibility in 
the area of environmental and occupational health. At 
the first meeting of the Joint Working Group on Health 
Cooperation held in Bethesda, Maryland, in February 
1981, NIH and Nigerian representatives shared their 
views on areas of specific interest for cooperation in 
biomedical research fields. 

Subsequently, a preliminary U.S. proposal was 
submitted to the Nigerian Ministry of Health as a basis 
for further consideration and refinement, and especial- 
ly to elicit Nigerian priority interests for incorporation. 
At the Joint Bilateral Economic Talks in September 1981, 
the Nigerian health representatives still had the propos- 
al under consideration. In the meantime, longstanding 
cooperation in several areas continues. 



19 



•Under the aegis of the U.S. -Romania Agreement on 
exchanges in education, culture, science, and technology, 
occasional exchanges in the health fields have taken 
place, primarily of U.S. specialists visiting counterparts 
in Romania. The major form of exchange continues to 
be the holding of joint biomedical research workshops, 
particularly in fields of cancer research, with the NCI 
being the principal partner on the U.S. side. After the 
last workshop in November 1980, in Romania, it was 
agreed that the next would be in the spring of 1982 in 
Bethesda, Maryland, on other aspects of cancer re- 
search. 

•The Interim Coordinators in biomedical research for the U.S. 
and Venezuela have been named. The U.S. Interim 
Coordinator visited Venezuela in July 1981 to hold 
discussions on implementation of the Memorandum of 
Understanding. On the basis of these discussions, the 
priority areas under consideration for collaboration in 
biomedical research are leprosy, Chagas' disease, 
cardiovascular disease, diarrheal disease, and mainte- 
nance of scientific equipment. No final decision has 
been made on these areas yet. Other areas to be 
explored are technology transfer of hybridoma and 
recombinant DNA research capacity, research man- 
power training, and epidemiology/clinical research. 

Other Liaison Functions 

In addition to monitoring and assisting in bilateral 
activities, the International Coordination and Liaison 
Program maintains liaison with WHO and PAHO and 
occasionally other multilateral organizations, and pro- 
vides the NIH positions on agenda issues for World 
Health Assemblies and the PAHO Directing Council 
meetings. The program provides material for the NIH 
participation as an observer in the European Medical 
Research Council meetings. Requests for services of 
NIH experts for WHO and PAHO committees and other 
purposes are processed with DHHS through 'the 
program. 

The program assists the Institutes by reviewing 
and clearing foreign travel notifications and by serving 
as a channel for cable communications to and from 
foreign embassies and the Department of State to NIH, 
by coordinating responses to inquiries on international 
issues, and by processing NIH foreign grants and 
contracts for clearance through the Department of 
State. 

The FIC Director meets periodically with interna- 
tional representatives of the NIH Bureaus, Institutes, 
and Divisions to exchange information and views on 
NIH international activities and to discuss implementa- 
tion of related policies and procedures. The meetings 
are organized by the program. 

The program collects information on NIH interna- 
tional activities and reports on these annually. It 
frequently prepares special reports about certain coun- 
tries as background for travel of an NIH principal or a 
visiting official; it also prepares comprehensive briefing 
books. 

The program serves as project focus for U.S. 
Government core support for the Gorgas Memorial 



Institute of Tropical and Preventive Medicine, Inc., and 
the Gorgas Memorial Laboratory in Panama provided 
through the FIC budget. 

The program also conducts special studies relevant 
to its responsibilities. The principal thrust of the special 
studies in FY 1981 was on collecting information on 
biomedical research resources and funding in indus- 
trialized countries in Western Europe, Australia, and 
Japan, and on compiling information on biomedical 
research institutions in the People's Republic of China. 
The first project was carried out by the Organization for 
Economic Cooperation and Development (OECD) 
under partial contract support by FIC. A report has been 
submitted and is under study. It is expected that this 
report will be circulated during FY 1982. 

The second project will lead to the publication in 
1982 of a directory to be used by American scientists and 
administrators planning to visit China or collaborate 
with Chinese scientists. It will contain names and 
locations of the institutions, directors, and laboratory 
chiefs, and selected recent publications from the 
institutions. 

During FY 1981, two books were published on 
health care: Rural Health in the People's Republic of China, a 
report by the Committee for Scholarly Communications 
with the People's Republic of China National Academy 
of Sciences, and Universal Free Health Care in Canada, 
1947-1977, by G. Hatcher, Albany Medical College of 
Union University. 

Gorgas Memorial Laboratory, Panama 

In 1928, Congress authorized a permanent annual 
appropriation to the Gorgas Memorial Institute of 
Tropical and Preventive Medicine, Inc., Washington, 
D.C., for the operation and maintenance of a research 
laboratory in Panama. This action, together with land 
and building donated by the Government of Panama, 
permitted the establishment of the Gorgas Memorial 
Laboratory (GML). Since FY 1971, the FIC budget has 
provided the annual U.S. core support funds, which 
amount to $1.8 million in FY 1981. The FIC maintains 
general program oversight for this funding. 

The laboratory conducts a diversified program of 
research on diseases prevalent in the tropics that are of 
importance to the United States, Panama, and the 
region. Particular emphasis is placed on virology, 
parasitology, and the effects of environmental change 
on disease vectors and transmission. In addition to 
conducting research, the laboratory makes its facilities 
available for visiting scientists and the training of 
professional personnel. It has cooperative arrange- 
ments with several U.S. universities for graduate and 
medical student body and course credit. Formal 
training courses in tropical medicine are conducted 
several times a year for U.S. Navy medical officers. 

For FY 1981, the Gorgas Memorial Laboratory had a 
number of substantial scientific accomplishments to 
report. Collaborative programs with the Yale Arbovirus 
Research Unit (YARU), the U.S. Army Medical Re- 
search and Development Command, the Ministry of 
Health of Panama, the Panamanian National Oncology 



20 



Institute, and the Centro Regional Universitario de 
David were continued. Specific activities for the year 
were in the following areas: 

• 'Acute hemorrhagic conjunctivitis (AHC): In cooperation 
with the Ministry of Health of Panama, GML provided 
virologic and serologic diagnosis and conducted a 
detailed seroepidemiologic survey for this disease, 
which caused an epidemic in Panama this vear. 
•Yellow fever: In cooperative research with YARU, 
vector mosquitoes were found to have substantial 
individual variation in their ability to produce, and, 
presumably, transmit, yellow fever virus. 
•Cancer registry: In cooperation with the Panamanian 
National Oncology Institute, GML has maintained the 
Panamanian National Cancer Registry since 1977. 
•Cervical cancer: As part of a detailed standardized 
Cervical Cancer Registry (which supplements the 
National Cancer Registry mentioned above), GML 
examined all discharge diagnoses, all hospital death 
records, and all operating room logs dated 1974 to 1980, 
from all hospitals in Panama City, Colon, Chiriqui, and 
Herrera Provinces, to ascertain all cervical cancer 
patients. A review of the hospital charts for all such 
cancer patients, beginning in 1974, was completed 
through 1979, with 1980 underway. A direct case- 
control study in Herrera Province has begun since data 
showed a high rate to be associated with birth in that 
province. 

•Sexually transmitted disease (STD): The GML STD 
program, in cooperation with the Ministry of Health, 
includes the newer recognized STD's as well as 
gonorrhea and syphilis. As part of this program, unique 
to Central America, GML in 1981 completed 



epidemiologic and sexual history interviews of 400 
workers, with blood samples from all, and endocervical 
cultures from 250. 

•Sandfly fevers: During 1980, infection with both Punta 
Toro virus and Chagres virus were demonstrated in a 
sample of some 2,000 sera drawn from U.S. military 
personnel in Panama. 

•Environmental assessment: As part of the environmental 
assessment project supporting the Tabasara hydroelec- 
tric project, GML completed a health status survey of 
over 4,000 residents of this remote area. 
•Diarrhea: This year a study was conducted comparing 
children hospitalized for diarrhea with unhospitalized 
rural children. In this pilot study, 1 percent of rural 
children harbored the pathogen for diarrheal disease 
(Campylobacter fetus jejune) , while 12 percent of children 
with diarrhea were positive. 

•Diphtheria: Forty-seven Panamanian medical students 
and 30 rural inhabitants were Schick-tested for diph- 
theria susceptibility. All rural inhabitants (ranging from 
13 to 64 years of age), but only 60 percent of the students 
(ages 19 to 23) were found to be immune. 
•Training: The course "Medicine in the Tropics," 
presented jointly with the U.S. Naval Medical Research 
and Training Unit located at GML, was given three 
times during FY 1981 to a total of 25 military medical 
officers, two students from the Uniformed Services 
University of the Health Sciences (USUHS), and one 
civilian medical student. The course was expanded to 
include a 3-day session on jungle survival. 

A complete annual report of the GML is prepared 
each year for the Congress. 



21 



NATIONAL CANCER INSTITUTE 



Introduction 

The prevention and control of cancer depends upon 
knowledge of causation, identification of population 
risk groups, availability of early detection measures, 
and the means for effective intervention. Throughout 
the world marked differences exist in the environmen- 
tal, occupational, and social conditions of people. Such 
factors are believed to significantly influence the 
incidence and course of many, if not most, types of 
cancer. Thus, the efforts of world specialists engaged in 
cancer research are stimulated and enhanced through 
international interaction, by collaborative studies, and 
by the exchange of scientific results. Through its 
participation in the international cancer scientific com- 
munity, the National Cancer Institute (NCI) ultimately 
benefits from the rapid advances in basic research 
throughout the world and their application to the 
clinical management, control, and prevention of cancer. 
The ultimate gain from such collaborative cancer 
research efforts between the NCI and international 
counterparts is a tangible improvement in the quantity 
and quality of health services to millions of people the 
world over. 

The contribution of NCI to the international 
struggle against cancer includes: (1) the continuing 
support of cancer research in foreign countries by 
highly qualified scientists; (2) the support of coopera- 
tive research programs, principally under bilateral 
agreements with foreign governments, institutions, or 
organizations; (3) the maintenance of liaison and 
research collaboration with international organizations 
and agencies that have well-defined objectives in cancer 
research and cancer prevention; (4) the support of 
training of foreign scientists in the United States as well 
as of the interaction of American scientists with 
colleagues in foreign laboratories; and (5) the manage- 
ment and operation of an International Cancer Research 
Data Bank for promoting and facilitating, on a world- 
wide basis, the exchange of information for cancer 
research, care and management of patients, and cancer 
control and/or prevention. 

Summary of Programs Activities: 
Bilateral Agreements and Other 
Country-to-Country Activities 

Cooperative cancer research programs under formal 



government-to-government treaties and other forms of 
bilateral agreements make up a major segment of the 
international activities of the National Cancer Institute. 
The first of these cooperative cancer research agree- 
ments was established on May 23, 1972, with the 
signing of the U.S. A.-U.S.S.R. Agreement for Coopera- 
tion in the Fields of Medical Science and Public Health. 
Subsequently, additional bilateral programs were for- 
malized between the NCI and the Japanese Society for 
the Promotion of Science (1974); the Institute of 
Oncology, Warsaw, Poland (1974), under the U.S. A.- 
Polish People's Republic Agreement; in 1975, with the 
French Institut National de la Sante et de la Recherche 
Medicale (INSERM) under an earlier NIH Agreement 
with INSERM; the Cairo Cancer Institute (1976), under 
the aegis of the agreement between the U.S.A. and the 
Arab Republic of Egypt; the Ministry of Science and 
Technology of the Federal Republic of Germany (1976); 
the Cancer Institute (Hospital), Chinese Academy of 
Medical Sciences, under the U.S. A. -People's Republic 
of China Accord for Cooperation in Science and 
Technology (1979); the National Cancer Institute of 
Milan and the Institute of Oncology of Genoa, Italian 
Republic (1980); and the National Institute of Oncology, 
Budapest, Hungary (1981). 

Egypt 

The effort between the NCI and the National Cancer 
Institute of Cairo University continued under the 
Special Foreign Currency Program (P.L. 480). Three 
ongoing programs include the treatment of bladder 
cancer, cytopathology of bladder cancer, and coopera- 
tive clinical studies, under the Southwest Oncology 
Group (SWOG), for the treatment of breast cancer, head 
and neck cancers, adult lymphomas, and childhood 
lymphoma. 

In 1981, the results were published on a joint 
American-Egyptian study, initiated in Egypt in 1976, for 
the evaluation of urinary cytology as a screening 
method for the early detection of bladder cancer in a 
rural community where the parasitic disease, schistoso- 
miasis, is endemic. Additional goals included the 
identification of a high-risk group related to schisto- 
some infestation and the determination of the preva- 
lence of urinary bladder carcinoma and its precancerous 
lesions in that population. In this study, the definition 
of the high-risk group proved to be valid since all 
tumors were detected among farmers in the high-risk 



23 



group; and, no tumors were detected among the control 
groups of the rural population. In farmers who work 
daily in the field, the schistosomal infestation, with 
frequent reinfection, is most intense. Nonf arming 
villagers, living in the same rural community, get 
milder forms of infestation often related to accidental 
contact during swimming or washing. This is consi- 
dered to be epidemiologic evidence of the relationship 
between schistosomiasis and urinary bladder cancer. 

Urine cytology, in this experience, proved to be an 
effective method for population screening. The yield of 
the screening was 11 cases of histologically confirmed 
carcinomas among 8,744 individuals screened. All 11 
cases were in the high-risk group; none were detected 
in the two low-risk control groups. A yield of two per 
1,000 of high-risk was obtained. This would also 
constitute a 4/10,000 of all rural population. And, 
knowing that about half of the population is below the 
age of 20, the prevalence rate could be estimated as 
8/10,000 of the rural adult population. 

Thus, the American and Egyptian scientists suc- 
cessfully concluded a joint project and demonstrated 
that a screening program is productive, if conducted in 
and restricted to high-risk groups. It is especially true in 
view of the limited funds, manpower, and medical 
facilities. 

Federal Republic of Germany 

An NCI delegation met in Heidelberg in April 1980 with 
a German delegation representing the German Ministry 
of Research and Technology and the German Cancer 
Research Center (DKFZ), to discuss formalization of 
bilateral cooperation on Environmental Carcinogene- 
sis. A Memorandum of Understanding was signed by 
the Director, NCI, and the Director, DKFZ, in February 
1981, for cooperative research on: the causation and 
mechanisms for carcinogenesis and the prevention and 
modulation of the carcinogenic process. 

In October 1980, a German delegation met with 
members of the NCI staff to discuss possibilities of 
cooperation in the areas of drug development and 
clinical studies. In addition to personnel and informa- 
tion exchanges, collaboration efforts are directed to- 
ward broadening the spectrum of tumor screening, 
beyond existing American and German models current- 
ly in use. This program is designed especially for the 
development of alkylating cytostatics. Human tumor 
xenografts are to be used for pharmacologic character- 
ization of new cytostatic agents. 

Another area of joint research relates to the 
synthesis and development of stabilized, "activated" 
oxazaphosphorine analogs (e.g., cyclophosphamide) 
with high toxic specificity and cancerotoxic selectivity, 
which can be used in local regional chemotherapy. The 
development of stabilized oxazaphosphorine analogs is 
of special interest for the improvement of systemic 
chemotherapy, especially where the goal is the selective 
destruction of tumor cells in conjunction with the 
transplantation of autologous bone marrow. There will 
be joint research on regional detoxification of anticancer 
drugs from the point of view of optimal detoxification of 
the drug for the benefit of normal tissues with 



simultaneous improvement in tumor chemotherapeutic 
efficacy. 



France 

In Paris, in December 1979, NCI agreed in principle to a 
French proposal for the reorganization of the American- 
French Program and combined the former Viral Oncolo- 
gy and Hormone/Cancer Working Programs into one 
which would be dedicated to Basic Research in 
Carcinogenesis. The other program deals with Clinical 
Cancer Research. 

The Clinical Cancer Research Program encom- 
passes the activities which were included formerly 
under the Clinical Trials and Treatment Research 
Program. However, the scope has been expanded to 
include immunotherapy, hormone therapy, and stu- 
dies on hormone receptors. Thus, the American-French 
clinical research effort includes: Phase I and II clinical 
trials and preclinical studies of the efficacy of anticancer 
drugs such as nitrosoureas, anthracyclines, and plati- 
num analogs; Phase III studies of gastrointestinal 
tumors; and the treatment of resistant breast cancer. 
Other collaborative efforts are devoted to the study of 
multiple pharmacologic and biochemical determinants. 

The program in Basic Research in Carcinogenesis is 
considered to be one of broad spectrum wherein 
meritorious scientific studies of a nonclinical nature are 
to be undertaken. These include such areas as cell 
proliferation, cell growth factors, normal and cancer cell 
differentiation, molecular genetics, tumor promoters, 
DNA repair, induction of cell transformation by DNA 
and RNA viruses, chemical and physical carcinogene- 
sis, etc. 

In October 1980, the Joint U.S. -French Committee 
on Basic Cancer Research met in Paris to review the 
activities of the past year and to plan for exchanges of 
scientists for fiscal year 1981. During the first 4 years of 
cooperation, 36 French scientists visited and studied in 
American laboratories, while 35 American investigators 
spent varying periods of time working in French 
laboratories. These collaborative efforts resulted in 
more than 35 joint publications. 

In view of increasing costs of travel and research 
expenses, the joint committee agreed that selection of 
exchange scientists will be based on the highest 
scientific merits and relevance to the goals of the 
cooperative program for mutual benefit. During the 
meeting, the French committee reported that 12 
research grants were made by the National Institute of 
Health and Medical Research (INSERM) to support 
cancer projects for collaborative research between 
American and French investigators. It was agreed that 
bilateral relationships would be very productive and 
elicit new avenues of research. The joint committee 
stressed the importance of the exchange of scientists to 
engage in collaborative research activities, to exchange 
techniques and research ideas, and to develop 
approaches to engender continuous interaction and 
cooperation. During the year, seven French scientists 
spent varying periods of time (a few weeks to 12 
months) in American laboratories, while seven Amer- 
ican investigators worked in French laboratories en- 



24 



gaged in basic research, particularly in molecular 
biology, biologic carcinogenesis, and hormone research 
related to cancer. 

The Joint NCI-INSERM Committee on Cancer 
Clinical Research met in Bethesda in December 1980 to 
review and evaluate the collaborative activities of the 
previous year. The meeting was cochaired by the 
Director, NCI, and a representative from INSERM. The 
discussion centered on the ongoing activities in clinical 
studies and treatment research. The joint committee 
agreed that the program area should be expanded to 
take advantage of unique developments that might 
arise in treatment research. This can be accomplished 
through the use of workshops to exchange ideas and 
clinical and experimental data, as well as scientist-to- 
scientist exchanges. 

The French committee reported that the committee 
was expanded to include other disciplines, such as 
epidemiology and radiation therapy, in order to cover 
areas which were not previously included. During the 
year, the French committee reviewed and selected 
proposals leading to 18 research grants for the support 
of collaborative research between American and French 
scientists. 

The joint committee agreed to form several work- 
ing groups: Working Groups for Clinical Trials; Clinical 
Biochemical Pharmacology; Biologic Response Modi- 
fiers; Radiation Therapy; and Epidemiology. These 
would meet to discuss areas of mutual interest for 
future collaborative efforts. There was general consen- 
sus to continue collaboration on the treatment of 
gastrointestinal cancers; clinical trials; pediatric oncol- 
ogy; new drug development; exchange of scientists for 
collaboration in clinical biochemical pharmacology; 
exchange of information in radiation therapy, including 
hyperthermia, radiosensitizers, labeled antibody, and 
time-dose delivery; and the exchange and coordination 
of information in the epidemiology study of nasopha- 
ryngeal cancer and high-risk cancer. 

During the year, three American cancer specialists 
and four French investigators were appointed as 
exchange scientists to engage in collaborative research. 

In February 1981, a French scientist was invited to 
attend the NCI-sponsored meeting on "Hybridoma 
Research," which was held at NCI. Also, two French 
investigators attended a "Workshop on T cells," held in 
Bethesda in June 1981. Several French oncologists also 
attended the annual meetings of the American Associa- 
tion for Cancer Research (AACR) and the American 
Society of Clinical Oncology (ASCO), which were held 
in Washington, D.C., in April 1981. 

Hungary 

A delegation of Hungarian cancer researchers visiting 
the United States in December 1978, and Americans 
visiting Hungary in June 1979, exchanged proposals for 
initiation of joint research between scientists of the two 
nations. Subsequently, on February 23, 1981, a Memor- 
andum of Understanding for a Cooperative Cancer 
Program was signed by the Director, NCI, and the 
Director, National Institute of Oncology, Budapest, 
Hungary. Priorities for scientific activity are given to 



studies in the areas of: Cancer Epidemiology/Etiology; 
Experimental Pathology; Immunology with emphasis 
on the Leukemias and Hematologic Research; and 
Cancer Therapy and Developmental Therapeutics. 

Implementation of activities under this agreement 
followed in September 1981, as two American immu- 
nologists journeyed to Budapest, and the NCI received 
three Hungarian specialists, each for 6 months. 

The American immunologists devoted their time to 
exchanges of information on: conditions under which 
receptors for immune globulins are shed from the cell 
surface and the nature, structure, and function of the 
shed receptors vis-a-vis those that are bound to the cell 
surface; natural killer (NK) cell activity in normal 
human donors and NK activity in patients with various 
types of cancer, especially breast and lung cancers; 
analyses of NK cytotoxicity and its possible utility for 
determining the prognosis in cancer patients; the 
production of high levels of alpha and gamma interfer- 
on from human peripheral blood leukocytes; and the 
production of a wide variety of monoclonal antibodies. 
They participated, as well, in a meeting on "Signal and 
Signal Processing in the Immune System." 

One of the Hungarian visitors, an experimental 
chemotherapist, is spending her time with colleagues at 
the NCI engaging in studies designed to investigate the 
resistance of murine tumor cells to alkylating agents 
utilized as anticancer drugs. Her work thus far has 
confirmed the role of glutathione, a tripeptide, in 
resistance to alkylating agents. She is now completing 
in vitro studies with buthionine sulfoximine, which is 
an inhibitor of glutathione biosynthesis. These studies 
have demonstrated that it is possible to completely 
sensitize the resistant cell to the cytotoxic effects of an 
anticancer drug such as L-phenylalanine mustard 
(L-PAM). L-PAM is one of the effective drugs, used in 
combination with others, for the treatment of breast 
cancer. 

The transplantation biologist/tumor immunologist 
from Hungary is spending his initial 4 months in the 
Sidney Farber Cancer Institute. His efforts are devoted 
to joint research on developing in endothelial cells 
monoclonal antibodies active against T cells and 
monocytes. His approach is to collect endothelial cells 
from the umbilical cord and collect the antigens acting 
against the monoclonal antibodies. At the same time, he 
is learning techniques for the separation of lymphocyte 
subcell populations and the differentiation of chronic 
myelocytic leukemia cells under conditions of a variety 
of stimuli. 

The third Hungarian scientist, an experimental 
pathologist/chemotherapist, took to Roswell Park 
Memorial Institute four human colorectal tumors 
transplanted in xenographic mice. He is using these and 
tumors obtained from RPMI patients to study methods 
of disaggregation — mechanical and enzymatic — to 
yield single-cell suspensions. At the same time, he is 
developing cell separation methodologies for biochemi- 
cal, biologic, and morphologic characterization of the 
various tumor subsets derived from the human cell 
suspensions. The subsets, then, are tested for their 
sensitivity to anticancer drugs. Thus, this segment of 



25 



American-Hungarian collaboration is considered to be 
mutually beneficial and constitutes a significant con- 
tribution to the clinical biochemical pharmacology 
programs ongoing in both countries. 

Italy 

Following upon the agreement reached in early 1980 for 
the pursuit of joint studies in Cancer Therapeutics and 
Cancer Prevention, a number of joint projects have 
been undertaken that have yielded some mutually 
beneficial results. 

In the Cancer Therapeutics area, an American- 
Italian workshop on "Clinical Biochemical Pharmacolo- 
gy" took place in Milan in November 1980. The 
objective of the session was to focus on opportunities 
for collaborative studies on, for instance, the heter- 
ogeneity of cancer disease and the need for individual- 
ized treatments determined according to the character- 
istics of each case. Another point of exchange was the 
relationship on cell sensitivity or resistance to an 
anticancer drug and the capacity of the cell to repair the 
DNA damage caused by the drug. An approach 
considered was the means for enhancing the binding of 
an anticancer drug, such as chlorozotocin, to the 
chromatin of the cell nucleus by steroids such as 
hydrocortisone. The latter was considered in light of a 
potential synergism of action between anticancer drugs 
acting as alkylating agents and the corticosteroids. 

Thereafter, cooperative relationships for joint ther- 
apeutic projects were established for studies on the 
treatment of breast cancer, Stages I-III, using new 
combinations of chemotherapy as well as the combined 
modalities approach; on the treatment of pain, nausea, 
and anorexia in pediatric cancer patients; on the 
biochemical-pharmacologic parameters of drug action; 
on new chemical analogs of Adriamycin and dauno- 
rubicin, which appear in preclinical tests to offer 
advantages in ' terms of efficacy of treatment and 
reduced cardiotoxicity in a broader spectrum of tumors; 
on biologic response modification, including use of 
thymic factors, interferons, monocloncal antibodies, 
and immunomodulation in a variety of immunity model 
systems; and on experimental metastases models, 
especially those related to membrane metabolism and 
cellular control of neoplastic growth. 

In the Cancer Prevention area, the U.S. -Italy Joint 
Committee met in Bethesda, in November 1980, to 
discuss areas for cooperative research, including: 
cancer epidemiology; chemical carcinogenesis; detec- 
tion and diagnosis; and biologic carcinogenesis. The 
mechanisms for implementation involve an exchange of 
scientists; an exchange of information and research 
resources; and the design and development of joint 
research projects. 

Currently, an Italian biologist is engaged in joint 
research in the Center for Experimental Biology, The 
Mount Sinai Medical Center. He is studying the 
relationship between polyamine synthesis and dif- 
ferentiation in an attempt to elucidate the biologic role 
of these compounds in the steps leading to differentia- 
tion of erythroleukemia cells in a model system 
developed at Mount Sinai. Polyamine biosynthetic 
enzymes appear to be involved in the differentiation of 



these cells. Thus, he is investigating the mechanisms of 
action of two enzymes, hoping to determine whether 
the appearance of specific biochemical markers of 
differentiation correlate with polyamine biosynthesis. 
These studies could shed some light on the cause of a 
"block in maturation" of malignant cells. 

An Italian epidemiologist spent 3 months in NCI 
working in the field of occupational epidemiology. 

And, at the Fox Chase Cancer Center, a young 
Italian physician is participating in the joint study of the 
interrelations of hepatitis B infection, iron metabolism, 
and primary hepatocellular carcinoma. Her contribu- 
tion to this project is clinical information and serum 
samples from parents and siblings of 125 Italian 
children who have thalassemia. Children with thalasse- 
mia, predictably, are at increased risk of becoming 
chronic carriers of hepatitis B virus and, hence, at 
increased risk of developing primary hepatocellular 
carcinoma. 

Japan 

In May 1979, the Joint American-Japanese Steering 
Committee restructured this cooperative cancer prog- 
ram to provide greater flexibility and breadth in order to 
accommodate current changes in the fields of cancer 
research. For the next 5-year period, the 11 research 
specialties being pursued jointly were categorized in 
four broad program areas: Etiology, Cancer Biology and 
Diagnosis, Cancer Treatment, and Interdisciplinary 
Research. 

The major objectives of the Etiology Program Area 
are to identify carcinogenic factors and to elucidate the 
mechanisms of carcinogenesis in an attempt to provide 
fundamental bases for understanding the cause of 
human cancer. This program includes four closely 
related subareas: epidemiology, chemical carcinogene- 
sis, viral carcinogenesis, and genetics. 

During this reporting period, key American- 
Japanese activities focused on scientific exchanges in 
the areas of biochemical epidemiology and chemical 
carcinogenesis. From discussions on the role of dietary 
factors in cancer causation, the need was established for 
new laboratory assays that might detect specific dietary 
constituents or metabolites in the urine, feces, or other 
body fluids. The basis for this determination is the 
questionable reliability of dietary histories and the need 
for identification of specific components of the diet. 

The recent discovery of the Japanese that "highly 
potent" mutagens can be formed during the broiling of 
fish provides a striking example of carcinogens associ- 
ated with nutritional habits. Discussions on the com- 
plexities of carcinogen metabolism highlighted the need 
for further assessing individual variation in humans. 

The development of antibodies to specific carcin- 
ogen-DNA adducts was highlighted as a potentially 
useful tool in the detection of human cancers through 
tissue sample analyses, providing a "dosimeter" of 
carcinogen exposure and metabolism. Highly sensitive 
methods of mass spectrometry and of combined liquid 
chromatography-mass spectrometry were reviewed 
from the viewpoint of being utilized to detect extremely 
small amounts of carcinogens in environmental sam- 
ples and body fluids (i.e., breast fluid or semen). 



26 



Epidemiologic and clinical findings related to T cell 
lymphomas were reviewed. The lymphomas appear to 
occur in clusters of high incidence in certain prefectures 
in Japan. It was interesting to learn that these cases 
show an abnormality of chromosome 14. Possible 
contributing factors include a mosquito-borne virus and 
a species of filaria. 

Discussions on tumor production revealed direct 
effects of saccharine on Concanavalin A agglutinability of 
rat bladder mucosal cells; the discovery of a specific 
membrane-associated receptor for the phorbol ester 
tumor promoters; and the discovery of a new, "highly 
potent" class of tumor promoters, teleocidin and 
Lyngbyatoxin, that are naturally occurring indole 
alkaloids. Lyngbyatoxin was found in edible seaweed. 
Teleocidin is a compound that has been isolated from 
Streptomyces. Both of these promoters demonstrate 
biologic activity against mouse skin and cell membrane 
receptor(s). 

During fiscal year 1981, two American and six 
Japanese investigators were appointed as Exchange 
Scientists in the Etiology Program Area. The scientists 
presented seminars and engaged in collaborative 
research activities in the areas of chemical and biologic 
carcinogenesis, molecular genetics, and epidemiology. 

Under the Cancer Biology and Diagnosis Program 
Area, a meeting was convened in October 1980, in 
Osaka, Japan, on "Immunology: Biology, Genetics, and 
Preclinical Immunotherapy." Seven American and 
more than 10 Japanese participants presented papers, 
providing significant advances in this area of inter- 
change. Within the field of basic immunology of 
host-tumor interaction, the topics of discussion in- 
cluded: the existence of tumor-specific antigens; the 
role of regulatory events in determination of host 
immune response to tumor; and the roles of cytotoxic T 
lymphocytes, macrophages, and natural killer cells as 
effectors of antitumor responses. Preclinical studies in 
experimental immunotherapy were also presented and 
dealt with areas of both tumor prophylaxis and active 
therapy. 

A conference on "Oncodevelopmental Proteins: 
Basic Biologic and Clinical Aspects" took place in San 
Diego, California, in December 1980. The information 
generated during this exchange between American and 
Japanese specialists is considered to be significant in 
advancing the state of the art in cancer immunology. 
Some of the highlights relate to Japanese experiences 
with horse antibodies (HA) to human or rat alpha 
fetoprotein (AFP). Although the HA's exhibit apparent 
cytotoxic effects on cultured hepatoma cells and 
transplanted rat hepatoma, only slight effects were 
observed in tests with human hepatoma or testicular 
tumors in nude mice. Japanese studies of the mechan- 
ism of AFP gene expression revealed that AFP synthesis 
is controlled at transcription with no indication, thus 
far, of the AFP gene during ontogenesis and oncogene- 
sis. Japanese scientists described the complexities of the 
dynamics of AFP in patients with hepatitis, liver 
cirrhosis, and hepatoma. In hepatoma, 64 percent 
showed highly elevated AFP values (> 10,000 ng/ml), 
whereas in chronic hepatitis, the levels are usually 



normal; cirrhosis (33 percent) exhibited modest eleva- 
tions of serum AFP. Two other observations were 
presented: administration of pyridoxine and ATP 
decreased AFP levels in persons with cirrhosis but not 
hepatoma; and the Con-A nonreactive fraction of AFP is 
less than 5 percent in patients with hepatoma, in 
contrast to 40 to 50 percent in patients with metastatic 
liver cancer. In viewing primary hepatocellular carcino- 
ma, Americans emphasized that: (1) geographic and 
sociologic differences relate to hepatitis B virus (HBV) 
status and the natural history of human hepatoma. 
Screening of susceptibility for hepatoma can now be 
considered by probing for integrated HBV DNA in 
patients' liver cells; (2) serum AFP is most useful in 
cancer detection when the lesion is not clinically 
obvious; (3) high serum ligandin (GSH transferase) 
levels appear to correlate with well-differentiated liver 
cancer, whereas high AFP correlates with less well- 
differentiated types. 

During the January 1981 symposium on "Genetic 
and Epigenetic Aspects of Cancer," in Honolulu, 
Hawaii, two general approaches were taken toward 
understanding the biology of cancer. The first involved 
the use of animal models to study the relative role of 
genetic and epigenetic factors in the development of 
cancer. The second approach involved the use of tissue 
culture systems to study the molecular basis of 
transformation by viral agents. 

During the year, two American and one Japanese 
investigators were appointed as exchange scientists 
under the Cancer Biology and Diagnosis Program Area. 

The Cancer Treatment Program Area continued to 
become progressively more multidisciplinary during 
the past year, balancing modality-oriented and disease- 
oriented seminars and exchanges. Radiation oncology 
continues to be of increasing importance in the 
exchange, as both countries work in the areas of high 
LET radiation, radiation sensitizers, radiation protec- 
tors, and hyperthermia. The exchange of information 
between American and Japanese scientists in this area is 
helping to advance the science more rapidly in both 
countries and is setting the stage for future collabora- 
tion. 

Chemotherapy still remains a major focus of the 
cancer treatment area. The exchange of drugs and data 
in the preclinical area is vigorous, aiding both countries 
toward more rapid progress. At the clinical level, a 
vigorous exchange continues as well. Based on the 
Japanese experience, clinical studies of Aclacinomycin 
A have begun in the U.S.A. Clinical studies here will 
soon begin on PEP-bleomycin, again based on the 
clinical experience in Japan. Both countries are placing 
emphasis on new anthracyclines, fluorinated pvrimi- 
dines, and nitrosoureas. From a disease-oriented 
perspective, emphasis is placed on tumors of the lung, 
breast, gastric area, and bladder. The results of the 
recently completed collaborative protocol in advanced 
gastric cancer between the Northern California Oncolo- 
gy Group and Japanese investigators has demonstrated 
comparability of Japanese and American data in the 
chemotherapy of this cancer. A second-generation 



27 



protocol has been developed and has just been 
activated. 

The "Breast Cancer Treatment Symposium," held 
in San Antonio, Texas, in March 1981, concentrated on 
the use of combination chemotherapy and endocrine 
therapy in the treatment of advanced breast cancer. The 
increased interest stems from the development of the 
estrogen receptor assay and of new hormonal 
approaches to the treatment of breast cancer, particular- 
ly the antiestrogen drug tamoxifen. The drug combina- 
tion therapy approach to breast cancer is now well- 
established in both countries. It is hoped that combin- 
ing the two modalities will dramatically improve 
survival. Chemotherapy data from Japan were pre- 
sented which correlated with the American data, 
indicating that the two countries were using drugs in a 
similar way and achieving comparable results. The data 
on hormonal assays in both countries demonstrated 
comparability as well. 

Two Americans and one Japanese were appointed 
as exchange scientists during fiscal year 1981 to share 
views on recent progress and stimulate further col- 
laboration in the Cancer Treatment Program Area. 

In the Interdisciplinary program area, a workshop 
was convened on "Differences in Lymphocytic Diseases 
between the U.S. and Japan," in Honolulu, March 
11-12, 1981. The meeting was based on the observation 
that high rates for lymphoproliferative disorders are 
associated with low rates of autoimmune diseases. 
Among U.S. whites, lymphoma occurs more frequently 
in males; autoimmune diseases occur more frequently 
in females (e.g., systemic lupus erythematosus [SLE] 
M:F-1:9, and Hashimoto's thyroiditis M:F-1:20). A 
reciprocal relation between the two categories of 
disease is also found when data from the U.S. and Japan 
are compared. Certain lymphoid neoplasms are rare in 
Japan, and certain autoimmune diseases are known or 
suspected to occur more frequently in Japanese than in 
Caucasians. As a result of this meeting, plans were 
made for several Japanese and American investigators 
to extend collaborative efforts to compare the frequency 
of SLE to other relatively common autoimmune dis- 
eases; to investigate rare cases of adult T cell leukemia in 
the U.S.; to study the distribution and determinants of 
subacute necrotizing lymphadenitis in Hokkaido; and 
to develop a hypothesis concerning ethnic differences 
in T cell function to account for the excesses and 
deficiencies in the lymphocytic diseases. 

During the year, a Japanese surgeon spent 6 
months at the Memorial Sloan-Kettering Cancer Center 
to study the recent advances in the diagnosis and 
treatment of pancreatic cancer, especially the technique 
for regional pancreatectomy. 

People's Republic of China (PRO 

During its meeting on November 19, 1980, in the PRC, 
the U.S. A. -PRC Joint Committee on Medicine and 
Public Health approved the joint cancer proposal which 
is included in Annex 2 to the U.S. A. -PRC Protocol for 
Cooperation in the Science and Technology of Medicine 
and Public Health. The American-Chinese cooperative 
cancer effort thus includes studies of the epidemiology, 
early detection and diagnosis, treatment, and multidis- 



ciplinary studies of esophageal cancer. 

In compliance with the provisions of the 1980 
cancer accord, the NCI has extended invitations to three 
Chinese principals for protracted periods of study and 
joint research in the NCI and other American cancer 
centers. One is to engage in studies of the use of 
endoscopy and other diagnostic procedures in cancers 
of the esophagus and lung. Research on the epidemiol- 
ogy of esophageal cancer and studies of technology for 
analytic epidemiology constitute the objectives of the 
second Chinese specialist. The third will pursue a 
program of study and research in cancer epidemiology 
and medical statistics. 

Under the aegis of the U.S. A. -PRC Protocol and 
during the interval of September-October 1981, five 
American scientists visited the People's Republic of 
China — two for periods of 2 weeks; two each for 4 
weeks; and the fifth for a period of 6 weeks. One of 
these traveled for the purpose of participating in 
workshops and teaching Chinese colleagues in the 
methods of organic and medicinal chemistry for the 
design and development of anticancer drugs, their 
preclinical testing, and potential utility in treating 
esophageal and other cancers. In this context, another 
of the American visitors intended to participate in 
scientific exchanges, principally in pharmaceutical 
institutes, on Chinese development of anticancer drugs 
and use of products of natural origin in the treatment of 
cancer. The third American was to engage in scientific 
exchanges on the relationship of dietary selenium to the 
incidence of esophageal and other cancers. Included in 
his program were discussions of chemical carcinogene- 
sis and nutritional factors as they may be related to 
cancer. Early detection of cancer, with particular 
emphasis on cytogenetic-epidemiologic, as well as 
pathomorphologic, analyses and technologies, were 
among the scientific topics to be pursued by the last two 
American visitors. 

Prior to the adoption of the 1980 U.S. A. -PRC 
collaborative cancer program, a joint NCI-Cancer 
Institute (Beijing) study was initiated in the area of 
biochemical epidemiology. The research embodies the 
collection and cultivation, in China, of human fetal 
tissues (liver, esophagus, stomach, and bronchi) for use 
in the identification of biochemical markers that may be 
associated with cancers of these organ sites. In tissue 
samples brought to the NCI by the Chinese collabor- 
ator, aflatoxin-Bi-DNA adducts have been isolated from 
liver samples taken from donors in cancer high-risk 
areas. This was done by use of monoclonal antibodies to 
aflatoxin B lr a technique developed by NCI scientists 
and taught to the Chinese. 

Poland 

The Agreement for Cooperation in Cancer Research 
was renewed, in April 1981, for an additional 5 years of 
collaborating effort between the National Cancer Insti- 
tute and the Maria Sklowdowska Curie Memorial 
Institute of Oncology. The accord has been a very 
important addition to the Polish National Cancer 
Program, in that it provides support for the exchange of 
information and scientific personnel. 



28 



During fiscal year 1981, Exchange Scientists from 
Poland included a molecular biologist who studied at 
the NCI; a radiologist who trained at Harvard Medical 
School; a surgeon who studied the treatment of 
gastrointestinal cancer at the University Hospital in 
Cleveland, Ohio; a physiologist at the National Heart, 
Lung, and Blood Institute; a pathologist who visited 
several leading American departments of pathology; 
and a radiotherapist at the University of Texas System 
Cancer Center. The Head of the Oncology Clinic, 
National Research Institute of Mother and Child of 
Warsaw, attended a conference on Pediatric Oncology 
in Washington, D.C., and later exchanged ideas with 
NCI staff on possibilities for cooperative research on the 
treatment of childhood cancers. 

An NIH senior scientist visited the Institute of 
Oncology in Warsaw to consult with the staff in the 
Department of Nuclear Medicine, relative to collabora- 
tive research in cancer detection. 

U.S.S.R. 

Joint American-Soviet cancer research activities during 
this fiscal year must be described as modest by 
comparison to previous years. In Moscow, U.S.S.R., 
from October 25 to 29, 1980, seven American scientists 
participated in a joint workshop on "Clinical Biochemi- 
cal Pharmacology." The American visitors were pro- 
vided with the opportunity to establish contact with 
excellent Soviet scientists with whom previous interac- 
tions had been relatively few. Some of the Soviet 
contributions were the result of their recent efforts with: 
(1) the selectivity of drug action and the administration 
of selectively localized drug-carrier complexes; (2) the 
selective activation of protective drugs and of protective 
metabolites; and (3) the biochemical and pharmacologic 
target-cell determinants of drug action for utilization in 
the design of "individualized therapy regimens." 

One Soviet virologist spent 1 month in NCI and the 
Sidney Farber Cancer Institute exchanging information 
on general problems associated with viral carcinogene- 
sis and/or cocarcinogenesis. 

A second virologist spent 6 months in the Sidney 
Farber Cancer Institute (SFCI) engaging in three 
research projects. The first of these related to a 
comparison of the genomes of two murine leukemia 
viruses. One of these viruses, the Akv virus, replicates 
well in animals, but does not induce disease. The 
second, the SL3-3 virus, also replicates in mice, but 
induces a rapid T cell leukemia. Electron microscopic 
analysis of the comparative structures of the two viruses 
indicate that they are closely related. The second topic 
dealt with the structure of the section of the human 
chromosome that contains sequences homologous to 
the transforming portion of the genome of the feline 
sarcoma virus. The third study was one begun by the 
Soviet visitor in his U.S.S.R. laboratory that deals with 
the structure of the viruses derived from the Soviet 
baboon colony in Sukhumi, Georgia. Jointly, the 
scientists applied methods developed in SFCI for 
detailed analysis of RNA virus genomes to the Soviet 
materials and were successful in defining the viruses. 
The second and third studies are continuing, in parallel, 
in the U.S.A. and the U.S.S.R. 



A Soviet geneticist spent 2 months at the State 
University of New York at Stony Brook for the purpose 
of mastering the technique of removing nuclei from 
cells and inserting these into the anucleated cytoplasm 
of cells of different origin. This enabled him and his 
American hosts to make "minicells" containing a few or 
a single chromosome and inserting these into cells of a 
different species. As a result, the Soviet scientist and his 
hosts were able to isolate and characterize a protein 
associated with cells that are resistant to genetically 
damaging agents such as colchicine. The concentration 
of the protein is directly proportional to variations in the 
length of the chromosome, which is amplified in the 
presence of an agent such as colchicine or methotrexate. 

During the "Sixth American-Soviet Review of 
Problem 03.03 — Malignant Neoplasia," September 13- 
22, 1981, proposals were discussed and, ultimately, 
agreement was reached to combine some of the existing 
programs under newly designated American-Soviet 
cancer priority areas and to discontinue, or limit, 
others. Thus, "Cancer Chemotherapy and Combined 
Modalities (Problem Area 03.0301)" is now designated 
as "Cancer Treatment." It will encompass activities 
related to Phase I and Phase II clinical trials; the 
exchange of preclinical and clinical drugs; collaborative 
studies on lung, breast, and ovarian cancers; and 
biologic response modification. Agreement was 
achieved by both sides to include the efforts currently 
under "Cancer Virology (Problem Area 03.0303)" and 
"Mammalian Somatic Cell Genetics Related to Neopla- 
sia (Problem Area 03.0304)" as major components of the 
newly titled area of "Carcinogenesis. "Select studies of 
chemical and physical carcinogens would be included 
as well. "Cancer Prevention" is the third new designa- 
tion, and would include some of the current joint 
studies in cancer epidemiology, pathomorphology, and 
end results of cancer treatment. Chemoprevention is 
likely to have special significance as a focus for future 
cooperative endeavors in large-scale clinical trials of 
agents currently considered to possess preventive 
activity. 

Activities with International Agencies: 
The International Cancer Research 
Data Bank (ICRDB) Program 

The ICRDB program, established by the National 
Cancer Act of 1971, has developed into an effective, 
multifaceted system for the rapid exchange of cancer 
research findings among scientists. This international 
resource for cancer information is comprehensive and 
of service to cancer researchers throughout the world. 
To facilitate the transfer of available cancer research 
information, the ICRDB program has: established three 
on-line computer data bases which enable scientists to 
retrieve cancer information at more than 2,000 locations 
within the United States and in 13 countries; developed 
a series of publications providing complete coverage of 
cancer research information, in special formats de- 
signed for easy use and quick reference; and supported 
a variety of specialized information collection, analysis, 
and dissemination activities. 



29 



The Computer Data Bases of the CANCERLINE 
System 

CANCERLIT, CANCERPROJ, and CLINPROT are the 
three data bases that make up the CANCERLINE 
System. 

CANCERLIT contains more than 275,000 substan- 
tive abstracts of information accumulated from pub- 
lished papers and those presented at scientific meet- 
ings, symposia, and conferences; books; technical 
reports; and research theses. CANCERLIT is growing at 
an annual rate of nearly 50,000 abstracts, selected from 
over 3,000 biomedical journals. Through monthly 
updating of CANCERLIT, the most recently published 
research results are quickly available to cancer research- 
ers worldwide. Since early 1980, all new literature 
entries have been indexed with the medical subject 
heading (MeSH) vocabulary developed by the National 
Library of Medicine (NLM), making their retrieval 
easier during on-line searching. ICRDB program 
screening, indexing, and abstracting activities are 
performed under contract by the Franklin Research 
Center in Philadelphia. 

Descriptions of some 20,000 current cancer re- 
search projects in 83 countries are the elements of the 
CANCERPROJ data base, the most comprehensive 
source available for ongoing cancer research project 
information. Included are nearly 6,000 foreign project 
descriptions collected by an international network of 
data input coordinators. Collection, input, and quarter- 
ly updating of the project descriptions in CANCER- 
PROJ are performed by the Current Cancer Research 
Project Analysis Center (CCRESPAC) under an inter- 
agency agreement with the Department of Commerce. 

Summaries of nearly 2,800 experimental cancer 
therapy protocols are the substance of CLINPROT, the 
data base providing worldwide access to information on 
new procedures, agents, and combinations of modali- 
ties/agents being evaluated for treating cancer patients 
in major American and foreign cancer centers. Collec- 
tion and input of protocol summaries and quarterly 
updating of CLINPROT are the contractual function of 
Informatics, Inc. 

The cancer information contained in the data bases 
of CANCERLINE is available through the computerized 
biomedical information network of the National Library 
of Medicine. Foreign access to the ICRDB has been 
enhanced by the recent addition of CANCERLINE to 
the EURONET system operated by a consortium of the 
major hosts in the European Community offering 
on-line scientific and technical information and interac- 
tive retrieval services. NLM's effort in CANCERLINE is 
supported by an intra-agency agreement. 

ICRDB Program Publications 

CANCERGRAMS are published monthly as current 
awareness bulletins containing abstracts of recently 
published literature in 66 major cancer research areas. 
Each month, CANCERGRAMS are compiled from 
carefully selected and organized abstracts screened 
from over 3,000 biomedical journals. They are prepared 
for publication by scientists at three Cancer Information 
Dissemination and Analysis Centers (CIDAC's). 
CANCERGRAMS enable scientists to keep up with the 



most relevant portions of the vast cancer literature with 
minimum time and effort. 

SPECIAL LISTINGS of current cancer research are 
annual compilations of ongoing research projects in 55 
different cancer problem areas. They are extracts from 
the CANCERPROJ data base, prepared by scientists at a 
Current Cancer Research Project Analysis Center. They 
are intended to stimulate interaction between investiga- 
tors pursuing related avenues of research. 

Ten to 20 ONCOLOGY OVERVIEWS are pub- 
lished each year. Each of the OVERVIEWS contains 
retrospective bibliographies, with abstracts, of recent 
literature and provides comprehensive coverage of 
specific topics of high current interest to cancer 
researchers. Included are the most relevant abstracts 
published during the past several years on the OVER- 
VIEW topic, providing indepth coverage of emerging 
foci of cancer research. OVERVIEWS are prepared by 
scientists at the CIDAC's, with review and editorial 
commentary by well-known researchers in each topic 
area. They provide a rapid means of updating knowl- 
edge in burgeoning areas of cancer research. 

The Compilation of Experimental Cancer Therapy 
Protocol Summaries 

Now in the 5th edition, 1981, the compilation is derived 
from the CLINPROT data base and contains over 1,500 
summaries of Phase II and Phase III clinical trials 
currently in progress in cancer centers of the world. The 
compilation is indexed by tumor, agent, and protocol 
identification number, and provides a useful reference 
for the practicing oncologist. Protocols which have been 
closed to patient entry during 1980 are listed by name of 
the principal investigator and include a mailing 
address. The 5th edition also includes a history of the 
Phase I protocols which were activated in 1980. 

The Directory of Cancer Research Information Re- 
sources, 3rd edition, 1981, contains over 900 entries 
covering the broad spectrum of resources available to 
health professionals. 

Special Information Activities of the ICRDB Program 

Three contract-supported cancer information dissemi- 
nation and analysis centers (CIDAC's) function as 
information resources in three broad areas of cancer 
research. These are the CIDAC for Diagnosis and 
Therapy, University of Texas System Cancer Center, M. 
D. Anderson Hospital and Tumor Institute, Houston; 
and the CIDAC's for Carcinogenesis and for Cancer 
Virology, Immunology and Biology, both at the Frank- 
lin Research Center, Philadelphia. Each CIDAC is 
staffed by scientists and served by a consultant network 
with special expertise in the appropriate fields. Within 
their own subject areas, CIDAC's prepare CANCER- 
GRAMS and ONCOLOGY OVERVIEWS, perform 
custom CANCERLINE searches, and provide scientific 
guidance to the ICRDB program. 

The current cancer research project analysis center 
(CCRESPAC) collects and processes ongoing research 
project information, generates the CANCERPROJ data 
base, and prepares the SPECIAL LISTINGS OF CUR- 
RENT CANCER RESEARCH. Custom data base 
searches are performed on request. 



30 



The Clearinghouse for Ongoing Research in Can- 
cer Epidemiology is a cooperative project supported 
jointly by the ICRDB program, the International 
Agency for Research on Cancer (IARC) in Lyon, France, 
and the German Cancer Research Center in Heidelberg, 
Germany. The CLEARINGHOUSE, located in Lyon, 
collects, processes, and disseminates detailed data on 
research related to cancer epidemiology and studies of 
human cancer causation in countries throughout the 
world. The CLEARINGHOUSE also prepares lists of 
epidemiology researchers and resources, responds to 
technical questions, and produces an annual Directory of 
Ongoing Research in Cancer Epidemiology. The 1981 
edition of the directory contains 1,313 abstracts of 
epidemiology projects in 80 countries. 

The Latin American Cancer Research Information 
Project (LACRIP) was developed through the ICRDB 
program in collaboration with the Pan American Health 
Organization (PAHO) and its Regional Library of 
Medicine (BIREME) in Sao Paulo, Brazil. LACRIP serves 
as the source for identifying, collecting, and supplying 
Latin American biomedical literature, summaries of 
ongoing cancer-related research projects, and active 
therapy protocols for inclusion in the CANCERLINE 
system. PAHO also serves as the center for searching 
ICRDB data bases and providing documents and data in 
response to requests for information from cancer 
researchers in Latin America. An automatic SDI service 
is also provided to cancer researchers and clinicians in 
Latin America. 

Through LACRIP, a series of collaborative clinical 
studies has been developed between nine cancer 
centers in the United States and six centers in Latin 
America. LACRIP maintains the clinical data gathered 
at the Latin American centers and arranges for the 
exchange of professional staff between centers in order 
to promote a better understanding of the current cancer 
treatments available in the United States. 

In cooperation with the the International Union 
Against Cancer (UICC), the ICRDB program provides 
partial support for a special Committee for International 
Collaborative Activities (CICA) within the framework 
of the UICC. One of the CICA activities is the collection 
of data on ongoing cancer research projects (including 
clinical protocols) from 72 countries. CICA personnel 
identify and promote collaborative projects among 
cancer centers and cancer scientists in different coun- 
tries. CICA periodically publishes an updated Interna- 
tional Directory of Specialized Cancer Research and Treat- 
ment Establishments, which contains descriptions of 
more than 700 of the world's cancer centers. An 
International Cancer Patient Data Exchange System 
(ICPDES) has been established as part of the CICA 
project. Present participants include nine European and 
five American cancer centers. The ICPDES is the first 
internationally recognized and standardized tumor 
registry, providing comparative data of value in cancer 
treatment and prevention from a multitude of coun- 
tries. 

Scientist-to-Scientist Communication 

The ICRDB program, through the UICC in Geneva, 



Switzerland, encourages international scientist-to- 
scientist communication through the International 
Cancer Research Technology Transfer program 
(ICRETT). This program promotes direct and rapid 
transfer of information about new or improved technol- 
ogy or methodology between investigators located in 
different countries. This is accomplished by supporting 
short-term visits for the purpose of conducting brief 
collaborative research projects by investigators working 
in different countries. Since the inception of the 
program in 1975, 534 ICRETT awards have been granted 
(through September 1981). 

In many instances, ICRETT associations between 
scientists from different countries develop into signifi- 
cant collaborative studies that otherwise might not have 
had the impetus and resources with which to evolve. 
For instance, an area of study known as "chrono- 
oncology" is attracting the attention and interest of 
many oncologists. The phenomenon relates to opti- 
mum timing of drug administration during the daily 
cycle, the 24-hour temperature pattern of tumors, etc. 
In this context, a chrono-oncologist and ICRETT 
awardee from the University of Minnesota journeyed to 
Chandigarh, India, to demonstrate radiation therapy 
and surgery-radiation therapy procedures and meth- 
odologies in the clinical management of cancer. He 
introduced the Indian oncologists to chronobiology 
(24-hour biology cycle) and chronochemotherapy and 
their relationship to immunobiology and immunother- 
apy. In the course of his visit, he arranged for his group 
to be consultants and to assist the Indian scientists ir 
the analysis of data emanating from their studies. 

Subsequently, an oncologist from Karnataka, In- 
dia, utilized the resources of his ICRETT award to study 
in the Chronobiology Laboratories of the University of 
Minnesota. He and his hosts collaborated on analyzing 
clinical data obtained in India for the tumor temperature 
patterns of carcinoma of the cervix. They then studied 
the effects of adrenocorticotropic hormone — ACTH — 
as pretreatment for improving patients' tolerance of 
Adriamycin when administered at certain hours of the 
day. 

A Liberian epidemiologist/biometrist observed and 
learned the principles for organizing a cancer registry 
during her period of ICRETT study in Dundee, 
Scotland. Her objective was to develop skills for 
improving methods in Liberia for the registration of 
new cancer cases and for followup studies of cancer 
morbidity/mortality. 

While in the National Cancer Institute, an ICRETT- 
sponsored Yugoslav immunologist studied techniques 
for the isolation, purification, and characterization of 
lung tumor-associated antigen. There now is a con- 
tinuous exchange of information on the results of the 
use of this antigen — a glycoprotein containing sialic 
acid — in the immunodiagnosis of human lung tumors. 

With the assistance of his ICRETT award, an 
epidemiologist from the People's Republic of China 
visited cancer registry facilities in Birmingham and 
Oxford, England, and Lyon, France, where he bene- 
fited from their design and experience with systems for 
registration of cancer incidence and followup. Of 



31 



importance to him was familiarization with methodolo- 
gies used to catalog and correlate information for use in 
studies of cancer risk factors and etiology. His training 
and application of it will be of significance in effective 
collaboration on problems of cancer epidemiology in 
progress under the American-Chinese Cooperative 
Cancer Program. 

The NIH Visiting Program 

During 1981, personnel of the National Cancer Institute 
served as hosts for scientists from 38 countries who 
came to the United States to engage in collaborative 
cancer research activities. There was a total of 244 
foreign visiting scientists, associates, and fellows. Nine 
of the visitors were appointed as Experts, and 42 came 
as Guest Researchers whose financial support comes 
from sources other than NCI. The activities of these 
scientists were pursued in the laboratories of the NCI 
Divisions of Cancer Treatment, Cancer Cause and 
Prevention, and Cancer Biology and Diagnosis. 

These associations are mutually beneficial. NCI 
host scientists are afforded opportunities to learn about 
cancer problems in a given foreign country; about 
factors peculiar to that nation that might be related to 
morbidity and mortality of cancer; and about activities 
under way concerning the management, treatment, 
and prevention of cancer. On the other hand, the 
foreign scientists are provided with unique opportuni- 
ties to improve their mastery of the scientific method or 
to develop their potential for significant contributions to 
basic and/or clinical research. The value of such 
scientific interaction can be assessed ultimately on the 
knowledge that cancer patients throughout the world 
are benefiting from an improved quality of care. 

Extramural Programs 

During 1981, the Divisions of Cancer Biology and 
Diagnosis, Cancer Treatment, and Cancer Cause and 
Prevention maintained extensions of their programma- 
tic objectives in foreign countries through 34 contract 
research activities, compared to 53 during the previous 
year. The Division of Extramural Activities provided 
fiscal support, through 52 grants, to scientists in foreign 
institutions conducting basic and applied cancer re- 
search. 

The Division of Cancer Treatment (DCT) 

DCT research contracts have been awarded to investi- 
gators in 11 institutions of six foreign countries for 
studies related to the characterization of anticancer 
agents; the search for potentially useful anticancer 
agents; the screening and testing of such compounds; 
and clinical trials on specific cancers. Examples of this 
international collaborative effort follow. 

In 1972, DCT established a "Cancer Chemotherapy 
Research Collaborative Office" at the Institut Jules 
Bordet in Brussels, Belgium. This facility provides an 
important service function to cancer researchers and 
clinicians in the U.S.A. and Europe as a center of 
reference for the vast amount of pertinent information 
on ongoing cancer research programs in both conti- 
nents. Its "liaison function" has been invaluable in 
promoting cooperative studies in experimental and 



clinical pharmacology and in clinical trials. In this 
context, there is a direct association with the European 
Organization for Research on the Treatment of Cancer 
(EORTC), which, among other activities, collects and 
manages data on clinical trials for Europe and serves as 
the coordinating center for clinical cooperative groups. 
By this means, the EORTC facilitates data collection, at a 
much faster rate, on the clinical evaluation of new drugs 
and therapeutic results from a large number of patients. 
Currently, there are approximately 64 clinical studies in 
progress among the EORTC clinical cooperative 
groups. Two hundred and fifty-five institutions in 13 
countries are involved in the trials and, currently, 6,500 
European patients are monitored by the EORTC data 
center. Since 1972, more than 25,000 new compounds 
have been collected through the direct efforts of the 
Collaborative Office, and several of these proved to be 
interesting enough for development toward clinical 
trial. 

DCT's maintenance in Tokyo, Japan, of a "Col- 
laborative Office for Cancer Chemotherapy Research" 
contributes significantly to NCI's cancer treatment 
program. On the order of 35 to 40 potentially useful 
drug materials are collected per month, including 
synthetic preparations and products of natural origin. 
During the period spanning June 1979 and June 1980, 
390 synthetics and 67 natural products were collected 
from 34 Japanese institutions. Active new materials 
include synthetic cyanines; analogs of 5-fluorouracil, 
cytosine arabinoside, and imidazolyl carboxamide; and 
nitrosoureas. Among the natural products are fatty acid 
esters of a crude nagilactone mixture, and anthracycline 
antibiotics. 

There is a continuation of cooperative preclinical 
and clinical research associations between American 
cancer centers and those of the United Kingdom, 
stimulated largely through DCT efforts and its partial 
support. The Institute of Cancer Research in London is 
contributing significantly to the DCT mission through 
research encompassing: drug development and 
screening; preclinical toxicology; clinical Phase I-II 
testing; drug rescue strategies and scheduling; and 
collaborative pharmacologic and clinical testing of new 
drugs. 

In Italy, DCT supports in part the coordinating 
center for clinical study of melanoma in the National 
Institute of Oncology in Milan. There, controlled 
clinical trials are continuing on breast cancer, gastroin- 
testinal cancer, and tumors of the brain. The Mario 
Negri Institute in Milan screens potential anticancer 
compounds that are available in Europe, emphasizing 
studies of their pharmacology. 

In association with the University of Dar Es Salaam 
in Tanzania, DCT is engaged in a study of the use of oral 
13-cis retinoic acid as a chemopreventive agent of skin 
cancer in albino Africans. These people, living in the 
equatorial zone, are subject to the most intense 
ultraviolet irradiation on the surface of the earth and are 
candidates, virtually, for a 100 percent increase of skin 
cancer. 

Three years ago, DCT entered into a cooperative 
relationship with Latin American cancer institutes by 



32 



virtue of the NCI-PAHO Collaborative Cancer Treat- 
ment Research Program (CCTRP). Clinical research 
activities are being pursued jointly by investigators in 10 
Latin American cancer institutes and hospitals and 8 
American cancer centers. Currently, there are 28 active 
treatment protocols being evaluated. These include 
therapeutic concepts in hematologic malignancies, 
childhood malignancies, osteosarcomas, and testicular 
cancer. Multimodal concepts in solid tumors are being 
pursued in advanced breast and head and neck cancer. 
Systemic therapy of solid tumors is being evaluated in 
advanced breast cancer, advanced gastric cancer and 
adenocarcinoma, and sarcomas. Since the inception of 
this multinational effort, 1,158 patients have been 
entered in the program. 

The Division of Cancer Cause and Prevention 
(DCCP) 

DCCP is very active in its associations with internation- 
al organizations and agencies which have well-defined 
objectives in cancer research, especially its cause and 
prevention. DCCP is engaged in collaborative contract 
research in eight institutions and agencies in six foreign 
nations. These foreign extensions of the DCCP program 
enable the Division to support fundamental studies on 
normal and malignant cells in relation to such carcino- 
gens as viruses and chemicals, as well as epidemiologic 
studies of human populations for the identification of 
risk factors predisposing to various cancers. These 
studies are primarily conducted under three major 
programs: Biologic Carcinogenesis; Chemical/Physical 
Carcinogenesis; and Epidemiology. Excellent model 
systems are available to scientists studying the effects of 
potentially carcinogenic factors in the environment. 

Contributions to the scientific advance in the 
Biologic Carcinogenesis program, for example, include 
the discovery of a DNA virus — Epstein-Barr virus 
(EBV) — provided impetus to a period of research to 
establish a causal relation to Burkitt's lymphoma (BL) 
and to nasopharyngeal carcinoma (NPC). Studies were 
focused on populatims of African and Asian patients, 
respectively, as sources for test materials. The emphasis 
was on the detection and incidence of BL cases in West 
Africa and the possible role of malarial infection as a 
contributing factor. NPC cases in the Hong Kong and 
Singapore regions of East Asia have been entered into 
the computer system of the International Agency for 
Research on Cancer (IARC) for analysis and determina- 
tion of whether certain genotypes place individuals at 
high risk to this cancer. Serologic tests for the detection 
of antibodies to various viral or viral-associated anti- 
gens in patients and controls continue to show a strong 
association of EBVwith lymphoproliferative disease 
and help define populations that are susceptible to its 
progression. 

Several investigations, under the Chemical Car- 
cinogenesis program, are designed to determine the 
mechanism of action of chemical and physical agents in 
the transformation and progression of a cell from the 
"normal" to the malignant state. These foreign studies 
are targeted toward the understanding of the interac- 
tion of activated metabolites of carcinogens with nucleic 
acids, both RNA and DNA, of the cell. Thus, they are 



attempting to define the mechanism of alkylation of 
N-nitrosamines and their derivatives and determine the 
DNA adducts generalized by exposure to ben- 
zo(a)pyrene and other hyjocarbon krcinogens. Other 
studies have long-range objectives for developing 
models to analyze and understand the steps in the 
carcinogenesis process by defining cellular preneoplas- 
tic changes in epithelial cells following exposure to liver 
carcinogens and developing short-term assays for the 
detection of chemical carcinogens. 

The Epidemiology program includes studies on the 
natural history of cancer in humans and on the 
incidence of cancers in different geographic locations so 
as to identify intrinsic and extrinsic risk factors. Many 
surveys are conducted in countries throughout the 
world, thus permitting comparison with the incidence 
of various cancers in the United States. Excess thyroid 
nodular disease, for instance, was detected following 
low-level exposure of children receiving X-ray therapy 
for ringworm of the scalp. Studies on the risk of 
developing second cancers among former cervical 
cancer patients given low-level doses of radiation 
suggest excess risks to other cancers such as bladder, 
rectal, kidney, and ovarian. 

Two new studies in the Epidemiology program 
hold the promise for highly significant information. 
One is a pilot study initiated to determine the basis of 
cancers of the esophagus and nasopharynx occurring in 
the populations within the People's Republic of China. 
The second relates to cancer incidence in various ethnic 
groups residing in Israel and for similar groups residing 
in the United States. It will permit the comparison of 
trends in cancer incidence among persons in two 
different geographic locations, and among second- 
generation immigrants. 

Among the notable activities in the Environmental 
Carcinogenesis program are the IARC Monographs on 
the "Evaluation of the Carcinogenic Risk of Chemicals 
to Humans." The 1980 compendium entitled, "Chemi- 
cals and Industrial Processes Associated with Cancer in 
Humans," serves as a source, for example, of the list of 
chemicals being tested for carcinogenicity in laborator- 
ies throughout the world. They reflect the international 
consensus on these agents and have become indispen- 
sable reference sources to scientific pursuits on carcino- 
genesis. 

The Division of Extramural Activities (DEA) 

Grants by the DEA have been made available to 37 
institutions and organizations in 13 countries. The 
scientific investigations include both basic and applied 
research. Among these are assays for and studies of the 
action of carcinogens and "promoters" of carcinogene- 
sis by personnel of the National Research Council of 
Canada. At the University of London, a study is under 
way on the therapeutic response of human tumor 
xenografts. At the University of Helsinki in Finland, 
studies are being pursued to determine glycoprotein 
differences in normal and malignant human blood cells. 
Scientists of the Weizmann Institute in Israel are 
engaged in research on the immunobiology of tumor 
metastasis. 



33 



NATIONAL EYE INSTITUTE 



Introduction 

Today, as many as 40 million people in the world are 
blind, and in 20 years, this number may double. Eighty 
percent of blindness is preventable or curable, and a 
major new international effort to eliminate blindness is 
under way. The National Eye Institute (NEI) is 
participating in the U.S. activities aimed at the preven- 
tion of blindness by evaluating and helping to establish 
the research base for development of effective preven- 
tion and treatment programs. Specifically, the NEI 
program is aimed at: 

•Obtaining sound epidemiologic data on the preva- 
lence of visual impairment and blindness. 
•Evaluating available health technologies, promoting 
programs that are the most cost-effective, and making 
these available to affected populations. 
•From this research, stimulating the controlled, clinical 
evaluation of findings which appear to be effective. 

Bilateral Agreements and Other 
Country-to-Country Activities 

India 

Meetings between U.S. and Indian scientists were held 
in Hyderabad, India, in October 1980 and in Bethesda, 
Maryland, in May 1981 to establish research protocols to 
be carried out at the center and develop the administra- 
tive structure of the Collaborative Clinical Research 
Centre for the Prevention of Blindness. 

Deficient nutrition is the leading cause of blindness 
in children worldwide. In India alone, 20,000 children 
become blind each year from nutritional deficiencies; 
10,000 of these children survive, and 10,000 die within 1 
year. However, the research base exists, primarily from 
work done in the U.S., to mount an applied clinical 
research program to identify those children who 
present the highest risk of going blind, determine ways 
to prevent this condition, and develop more cost- 
effective programs so as to target vitamin A to the 
highest risk populations. Such a program has been 
established, culminating in a series of workshops held 
over the past year in India and the U.S. This has 
resulted in the establishment of a Collaborative Clinical 
Research Center for the Prevention of Blindness at 
Hyderabad, India. The following is a list of projects to 
be carried out jointly in the center: 
•Relationship between measles, keratomalacia, and 



blindness in children. 

•Effect of ascariasis and deworming on vitamin A 
nutritional status of children. 

•Anterior segment collagenase activity and keratoma- 
lacia. 

•Absorption of vitamin A in diarrhea, treated with or 
without oral rehydration solution. 
•Immunity and infection in relation to vitamin A status. 
•Evaluation of the relative dose response (RDR) for 
identifying subclinical vitamin A deficiency in children. 
•Case control study of xerophthalmia in children. 

Final approval of the research agreement formaliz- 
ing this arrangement has been received from the 
Government of India and is pending on the U.S. side. It 
is expected that the Center will commence operations in 
early 1982. 

Japan 

The U.S. -Japan Memorandum of Understanding 
(MOU) on Vision Research has been ongoing since 
April of 1976. The MOU provides for an exchange of 
scientists between the National Eve Institute and the 
Japan Society for the Promotion of Science. Two 
scientists per year from each country may be selected 
for the exchange — one short-term (2 weeks to 3 months) 
and one long-term (3 months to 1 year). 

The stated objectives of the MOU are to foster 
better communications and interactions between vision 
research scientists in Japan and the U. S. ; to broaden the 
base of vision research through cooperative efforts; and 
to bring about better utilization of existing resources for 
vision research in both countries. Through the ex- 
change of scientists, the objectives were accomplished 
in 1981. 

In October 1981, a scientist from the University of 
Tokyo, joined a scientist from the NEI in the investiga- 
tion of transport system in the anterior uvea for 
nonsteroid weak acid anti-inflammatory agents. The 
Japanese scientist proposed to study the time course of 
the accumulation of radioactive aspirin or other non- 
steroid anti-inflammatory agents in the isolated ciliary 
body, the saturation kinetics of the accumulations, and 
the effects of certain agents. He will study how the 
above transport system is related to the intra-ocular 
pharmacokinetics of such agents in in vivo condition. 

Another scientist from the University of Tokyo 
spent November visiting major eye research centers 
and exchanging information on the fine structure of 



35 



photoreceptive membrane and on the plasmalemmal 
specialization of retinal cells in cuttlefish. 

There were two short-term American visitors to 
Japan in 1981. The first, from Case Western University, 
spent a month each at the Kobe University Medical 
School and the University of Kyoto and attended the 6th 
International Symposium on Glycoconjugates. He 
pursued structural studies on the oligosaccharides of 
glycoproteins and glycolipids and worked with the 
culture of cells from the neural retina and retinal 
pigmented epithelium. The second, from the Universi- 
ty of California, visited the Kanazawa University to 
conduct studies of plasticity of single cortical neurons 
during physiologic study. Earlier studies in amblyopia 
and strabismus using animal models were continued 
and analyzed. 

The Memorandum of Understanding will be 
negotiated for a 3-year renewal in April 1982, as both 
parties feel this program to be a valuable exchange. 

U.S.S.R. 

A meeting to review progress on the Vision Research 
Section of the U.S. -U.S.S.R. Program for Health 
Cooperation was held in October 1981 between the 
Director, NEI, and the Director, All-Union Research 
Institute of Eye Diseases. Considering the magnitude of 
public health problems caused by eye disease and the 
knowledge and research accomplishments of investiga- 
tors in the United States and the Union of Soviet 
Socialist Republics, the need for continued collabora- 
tion on vision research aimed at the prevention of eye 
diseases and blindness and the alleviation of suffering 
caused by these diseases was reaffirmed. Progress in 
each problem area was documented in 1981. These 
areas are: 

•Use of Q-s witched laser in the treatment of glaucoma. 
•Assessment of critical flicker fusion (CFF) to determine 
optic nerve function. 

•Assessment of gratings to determine optic nerve 
function. 

•Clinical trial of ENKAD treatment of retinitis pigmen- 
tosa. 

Activities with International Agencies 

World Health Organization (WHO) — A Programme 
for the Prevention of Blindness 

The Director, NEI, continued to serve as a member of 
the World Health Organization's Special Advisory 
Panel on the Programme for the Prevention of Blind- 
ness. This group has been established to advise WHO in 
its efforts to eliminate blindness worldwide. The 
advisory group held its annual meeting in New Delhi, 
India. The major areas discussed were: 
•The economic implications of blindness prevention. 
•Activities of collaborating centers for the prevention of 
blindness. 

•Research priorities in the Programme for the Preven- 
tion of Blindness. 

The Programme for the Prevention of Blindness, 
which is primarily supported by the National Eye 
Institute, has expanded its collection of data on 
blindness and its causes over the past year. Several 



additional blindness surveys are being developed in 
Asia and Latin America in addition to the survey plans 
in Mali and Togo that were developed in 1981 and will 
be carried out in 1982. 

Activities of NEI as a WHO Collaborating Center 

The NEI continued to serve as a WHO Collaborating 
Center for the Prevention of Blindness. The functions of 
this center were: 

•To provide facilities for the training of personnel in 
epidemiology and biostatistical techniques. 
•To conduct applied field research on the epidemiolo- 
gy, management, and operational aspects of avoidable 
blindness. 

•To foster a multidisciplinary approach to the promo- 
tion of eye health and to delivery of eye health care to 
all. 

•To participate in the collection, evaluation, and 
distribution of pertinent information. 
•To provide advisory services and expertise on request. 
•To conduct research into low-cost, innovative 
approaches to conduct surveys of blind and visually 
impaired persons. 

Specific activities carried out in 1981 were: 

Workshop on Operations Research and Mobile Camp 
for Cataract Surgery 

In October 1980, a workshop was held on operations 
research and mobile camps for cataract surgery. The 
Director, NEI, was a major organizer and contributor to 
this meeting. The workshop examined the feasibility of 
applying techniques of operations research in India, 
where 1.5 million people go blind every year, and 
where 6 million people are blind from cataracts. Various 
mathematical models for solving this problem were 
discussed as well as organizational approaches. An 
operations research approach was viewed as most 
promising by the participants, and demonstration 
projects to test various models will be developed. 

Evaluation of a Research Program in Eye Health for 
the Government of India 

The National Eye Institute provided a short-term 
consultant to the Government of India to: 
•Review the recommendations of the National Group 
on Research in Eye Health and ICMR Advisory Panel 
and Ophthalmic Sciences. 

•Formulate project protocols for research on problems 
identified for priority attention. 

•Recommend collaboration with national and interna- 
tional workers and institutions. 

•Identify and select resources for implementing the 
research activities. 

Strategic Approaches to Prevent Blindness 

The NEI is providing planning expertise to the WHO in 
the development of strategic approaches to prevent 
blindness. This is the first stage in the development of a 
planning framework in which an accelerated and 
expanded international prevention of blindness pro- 
gram should operate. The areas of emphasis are 
cataract, trachoma, onchocerciasis, nutritional blind- 
ness, ocular trauma, and glaucoma. 



36 



European Office of WHO Meeting on the Use of 
Residual Vision by Visually Impaired Disabled 
Persons 

The NEI participated in a multidisciplinary meeting, 
consisting of representatives of national research orga- 
nizations, professors of visual science, ophthalmolo- 
gists, representatives of private societies for the visually 
disabled, and WHO staff members, to review the status 
of services and research in the field of visual impair- 
ment. The categorization of visually impaired disabled 
and handicapped persons still presents conceptual and 
organizational difficulties. The meeting therefore dis- 
cussed criteria for the categorization of persons with 
residual vision, assessment of their number, and the 
different problems they face. Special attention was paid 
to the availability and assessment of existing technology 
and to the need to develop appropriate and simple 
technology which would enable people with residual 
vision to maintain their independence. The nature of 
existing services and the available manpower were also 
reviewed with the aim of filling gaps as perceived by 
both professionals and consumers, and to formulate 
recommendations for action in the context of the 
International Year for Disabled Persons and interdisci- 
plinary research in priority areas. 

WHO Consultant 

The NEI hosted a scientist from the Department of 
Biochemistry, Institute of Post Graduate Medical 
Education and Research, Calcutta, India. As a consul- 
tant at the NEI, he engaged in cooperative research 
activities aimed at the application of advanced biochem- 
ical techniques to the development of new diagnoses 
and treatment approaches for children suffering from 
nutritional deficiencies. Specifically, he was able to 
work with U.S. experts on techniques of tubulin 
biosynthesis and microtubule assembly in normal and 
vitamin A-deficient animals exhibiting kerophthalmia. 

Clinical Trial of Steel Sutures 

NEI staff have been assisting in the development of a 
randomized clinical trial involving approximately 4,000 
patients assigned to either conventional or vanadium 
stainless steel sutures in cataract surgery. The study is 
planned to be conducted in India, and will evaluate the 
safety and efficacy of this suture material, and its 
potential for reducing the postoperative stay. There is a 
large backlog of cataract cases awaiting surgery in India. 
If steel sutures prove effective and also permit shorten- 
ing of the postoperative recovery period, then this 
backlog can be reduced. 

Development of a Cataract Instrument 

NEI intramural scientists, Indian scientists from the 
Aravind Eye Hospital in Madurai, and engineers from 
the National Aeronautics and Space Administration 
have been working for several years to develop a more 
effective instrument for removing cataracts. This in- 
volves developing and evaluating a technique for 
removal of hard cataracts through a small incision with 
an air turbine device. During the past year, the 
technique and the instrument have been refined and 



successfully tested in animals and on hard cataracts 
from Indian patients in vitro. Trials have been initiated 
on a series of blind eyes with hard lens in India by 
Indian ophthalmologists on the research team. This 
instrument and surgical technique have great potential 
for shortening the postoperative recuperative period for 
cataract patients, which has been one of the principal 
logistical problems in making cataract camps and 
mobile units more effective. The next steps are the 
simplification and miniaturization of the tool. 

WHO Immunology Course 

NEI scientists participated in the Immunology Course 
which took place at WHO Headquarters in Geneva and 
in Epalinges. This course presents a unique opportunity 
to contact the finest Third World immunologists. Before 
this NEI participation, there was no aspect of ocular 
immunology touched upon in the course. The course 
provided an opportunity to present various aspects of 
ocular autoimmunity, ocular immunoregulation, and 
ocular parisitic diseases. It is hoped that the course will 
kindle enough interest in further research, since major 
problems in the Third World — onchocerciasis, leprosy, 
and toxoplasmosis — all have ocular manifestations. 

Health Scientist Exchange Programs 
and NIH Visiting Program 

Visiting Scientists in the NEI Intramural Program have 
contributed to a number of major advances made in 
vision research. The enzyme aldose reductase appears 
to be involved in the initiation of a number of diabetic 
complications. Visiting Scientists were actively in- 
volved in experiments in which aldose reductase 
inhibitors were used in preventing cataracts and 
ameliorating the adverse diabetic effects on the catar- 
acts. 

Another major area in which Visiting Scientists are 
involved is in the research in ocular immunology. 
Uveitis is a major ocular problem in that rational means 
of treatment have not been developed. NEI scientists 
have made significant advances in developing a mode 
of treatment for certain types of uveitis. 

The Visiting Scientists program has been invalu- 
able to the Intramural Program because it serves as a 
means of attracting top scientists and ophthalmologists 
who have special expertise. They have enhanced the 
intellectual environment of the Institute. 

Other Extramural and Intramural 
Support 

The extramural and intramural components are sup- 
porting epidemiologic and biomedical research in the 
areas of cataract, corneal infections, and the develop- 
ment of new drug therapies that have great potential for 
preventing or treating these diseases. Especially impor- 
tant here are the investigations into the relationship of 
vitamin A to nutritional blindness, which could result in 
the near future in clinical applications that will help 
prevent this leading cause of childhood blindness 
worldwide. 



37 



NATIONAL 
HEART, LUNG, AND BLOOD 

INSTITUTE 



Introduction 

The National Heart, Lung, and Blood Institute's 
(NHLBI) programs in heart, blood vessel, lung, and 
blood diseases and blood resources are receiving 
worldwide attention. These disease problems are of 
major significance and are shared to a greater or lesser 
extent by both industrialized and developing nations. 
Recent international statistics show dramatic shifts in 
the patterns of these diseases throughout the world. For 
instance, table below shows selected statistics compar- 
ing the United States with other councttries in trends of 
cardiovascular disease, the number one cause of death 
in the United States and many other countries. The 
U.S.A. currently leads the world in the rate of decline of 
coronary heart disease. This is a marked change in view 
of earlier epidemic increases in cardiovascular deaths 
over many decades. 

In recent years, there have been major changes in 
the initiation and development of the Institute's 
international activities. As a result, international pro- 
grams and activities have expanded significantly. Three 
factors have played important roles in this develop- 
ment. First, the National Heart, Lung, and Blood 
Program mandated by the President and the Congress 
in 1972 has significantly broadened the scope and depth 
of the Institute's national programs, thereby providing 
new opportunities for meaningful international col- 
laborative efforts. Second, the Department of Health 
and Human Services and the Department of State have 
encouraged the strengthening of international coopera- 
tion in medicine and health. Third, the scientific and 
medical leadership of many other countries has shown 
an increased interest in the Institute's programs and 
activities and in efforts to enhance international col- 
laboration, particularly in the cardiovascular area, but 
also increasingly in the lung and blood diseases areas. 
Increased international attention to the Institute's 
programs has been catalyzed by the recent success in 
the United States in bringing about a significant decline 
in cardiovascular disease. 



International Trends in Mortality Rates 
for Coronary Heart Disease 
Age-adjusted, Males Age 35-74 Years: 
Selected Countries 1977 and 1969 



Rate per 100,000 


Population 




Difference in 


Country 


1977 


1969 


Death Rate 


U.S.A. 


650.4 


864.7 


Decrease 214.3 


Australia 


649.0 


843.7 


194.7 


Israel 


522.8 


653.3 


130.5 


Canada 


624.1*** 


703.3 


79.2 


Norway 
Japan 


540.6 
99.2 


583.0 
123.3 


42.4 
27.1 


New Zealand 


747.1*** 


773.4 


26.3 


Belgium 


426.8*** 


446.1 


19.3 


Finland 


878.0** 


893.7 


15.7 


Italy 


309.6* 


313.0 


3.4 


Czechoslovakia 


590.3* 


587.9 


Increase 2.5 


France 


207.0** 


195.2 


11.8 


Netherlands 


493.4 


478.7 


14.7 


Denmark 


584.6 


566.1 


18.5 


England/Wales 


685.6 


662.1 


23.5 


Switzerland 


320.8 


290.4 


30.4 


Austria 


460.1 


428.3 


31.8 


Germany (FR) 
Yugoslavia 


466.1 

227.6*** 


427.3 
185.0 


39.3 

45.6 


Sweden 


587.6 


524.0 


63.6 


Romania 


248.2 


170.5 


77.7 


Hungary 
Bulgaria 


532.5 
423.5*** 


441.6 
299.4 


90.9 
124.1 


Poland 


319.8 


186.5 


133.3 


* 1976 

" 1975 
«» 1977 







Source: Center for Health Statistics (ICD 410-413 Unpublished) 



Broad Goals 

The NHLBI, in addition to supporting a vigorous 
national program of research, prevention, and control 
of heart, lung, and blood diseases, also maintains an 
active and open exchange of scientists and information 
with many countries whose health problems are similar 



or related to our own. 

The broad goals of the National Heart, Lung, and 
Blood Institute's international programs and activities 
are: 

•To develop international activities relevant to the goals 
and priorities of the U.S. national programs in heart, 



39 



lung, and blood diseases and blood resources. These 
goals are set forth in the Institute Director's annual 
report to the President and the Congress on the 
National Heart, Blood Vessel, Lung, and Blood 
Program. 

•To develop international contacts, activities, and 
programs of mutual interest and benefit to the United 
States and to the cooperating country or countries in 
areas related to the Institute's national mission. 

Thus, the scope of the Institute's international 
activities and programs closely follows the scope of the 
Institute's national programs and priorities. 

The broad goals of the NHLBI international 
programs include the design and implementation of 
international population studies, clinical investiga- 
tions, and laboratory experiments to enhance and 
complement data generated in domestic studies on 
important aspects of heart, lung, and blood diseases 
and blood resources. As a result of this broadened 
scientific perspective, it is possible for U.S. and foreign 
scientists to develop joint international data bases and 
to draw international comparisons not possible with 
national studies alone. These international compari- 
sons are important in understanding disease and in 
developing new approaches to treatment, prevention, 
and control. 

With some countries, joint studies are designed for 
implementation by U.S. and foreign scientists with 
complementary skills, approaches, or facilities for 
studying the same problem. This leads to more 
cost-effective utilization of NHLBI funds to support 
research in particular areas. The experience of the 
NHLBI international programs supports the conclusion 
that some studies can be performed less expensively in 
other countries than is possible in the United States. 
The Institute seeks to maximize the scientific benefit 
from available research dollars by taking advantage of 
such opportunities for international cooperation, when 
offered by other countries. 

The NHLBI international programs also focus on 
the discovery and analysis of new methods, treatments, 
techniques, and equipment which could be applied 
effectively through the U.S. biomedical research com- 
munity, to the ultimate benefit of U.S. health care 
consumers. This goal is facilitated by international 
exchanges of information and data which offer clues to 
productive directions for further research and develop- 
ment. 

Specific Impacts 

Several recent international developments are likely to 
affect the future direction of the Institute's international 
programs. First, cardiovascular disease is the major 
health problem in many countries in the world, and 
concerted international action is being taken to deal 
with it. The Institute plans to continue to cooperate in 
these efforts. Second, developing nations are con- 
cerned that appropriate technology be introduced to 
deal with cardiovascular and other health problems in 
their countries, and the Institute has indicated an 
interest in increasing collaboration with these coun- 
tries, keeping this goal in mind. Third, the designation 



in 1980 of the NHLBI as the WHO Regional Collabora- 
tive Center for Research and Training in Cardiovascular 
Diseases for the Americas is likely to open up new 
opportunities for multilateral cooperation with Latin 
American countries as well as for the rest of the world. 
During the past few years, many cardiovascular 
studies in the United States and other countries have 
indicated marked changes in the risk of cardiovascular 
disease among persons who migrate from one country 
to another, and among those who experience rapid 
"Westernization" in their home country. These findings 
have tremendous implications for public health. Be- 
cause these changing patterns have occurred within 
relatively short time periods, they are evidence of 
environmental and lifestyle influences. It therefore 
follows that if we can define these environmental 
circumstances more precisely, we would open new 
pathways to disease prevention. Thus, it is anticipated 
that further international cooperation on the epidemiol- 
ogy of cardiovascular disease will benefit populations 
both in the United States and abroad. There is reason to 
believe that the answers to these disease problems will 
come more rapidly through carefully targeted interna- 
tional cooperative research on populations that vary 
widely in lifestyle, nutrition, and susceptibility. 

Bilateral Agreements and Other 
Country-to-Country Activities 

Canada 

A major Institute activity is the carrying out of 
multicenter controlled clinical trials aimed at validating 
treatment or prevention of cardiovascular and pulmon- 
ary diseases. The following clinical trials have a major 
participating center located in Canada: The Beta Blocker 
Heart Attack Trial, the Coronary Artery Surgery Study, the 
Lipid Research Clinics, the Multiple Risk Factor Intervention 
Trial, the Clinical Study of Intermittent Positive Pressure 
Breathing, the Nocturnal Oxygen Trial, and the Prevention 
of Neonatal Respiratory Distress Syndrome with Antenatal 
Steroids Administration Trial. The Institute has also 
funded Canadian research aimed at modifying the 
development of atherosclerosis in rabbits by blocking 
the activity of the amino acid lysine in circulating 
lipoproteins through the use of drugs or dietary 
manipulation. 

France 

Under the NIH-INSERM (Institut Nationale de la Sante 
et la Recherche Medicale) Agreement signed in 1970, a 
3-year cooperative study on interstitial (fibrotic) lung 
diseases was initiated in 1980 by intramural NHLBI 
researchers and their colleagues in Paris. Because of the 
increased frequency of interstitial lung disease during 
the past two decades, this problem is receiving 
increased attention among scientists. The U.S. -France 
exchange program in this area was established to share 
scarce patient biopsy materials, thereby making it 
possible to undertake a variety of large-scale studies on 
the pathology of these diseases. The incidence and 
significance of Langerhans cells in lungs of more than 
100 patients with various types of pulmonary fibrosis 



40 



have been studied, and the results have been pub- 
lished. A study on histiocytic disorders and another on 
hypersensitivity pneumonitis are completed, and the 
results have been submitted for publication. Other joint 
projects being pursued at the present time include: a 
general review and revision of the criteria for the 
diagnostic classification of interstitial lung disorders on 
the basis of histological and electron microscopic 
findings; studies of the ultra structure of Langerhans 
cells in histiocytosis S; studies of pulmonary ultrastruc- 
ture in sarcoidosis and other diseases in which 
granulomas develop in the lung; ultrastructural studies 
of the pulmonary vasculature in interstitial lung 
diseases; and studies of the morphology of abnormal 
collagens found in diseased lungs. All of these studies 
have been made possible by the pooling of materials 
and the collaboration of U.S and French researchers. 

Under the auspices of the NIH-CNRS (Centre 
Nationale de la Recherche Scientifique) Program for 
Scientific Collaboration, a young U.S. physical 
biochemist spent 8 months investigating an important 
area of lipoprotein structure and function at the CNRS 
Center for Molecular Biology in Orleans. She studied 
mechanisms by which serum lipids and apolipopro- 
teins interact to form the stable native lipoproteins that 
circulate in the blood. The results of this research 
provided further insight into the atherogenetic process 
and the protective role of high-density lipoproteins 
against plaque formation. 

The NHLBI has initiated a Primary Reference 
Materials Program for hemocompatible materials to be 
used in cardiovascular prostheses. French researchers 
working in the biomaterials area have requested that 
they receive such reference materials when these 
become available. 



Federal Republic of Germany (FRG) 

The U.S. -FRG cooperative activities in the cardiovascu- 
lar area are conducted under the auspices of a Joint 
U.S. -FRG agreement between the DHHS and the 
Federal Ministry for Research and Technology of the 
Federal Republic of Germany on Cooperation in the 
Field of Biomedical Research and Technology. The 
original 5-year agreement in 1976 was extended for 5 
years in 1981. The emphasis is on linking ongoing 
projects in the two countries in two areas: arterioscler- 
osis and hypertension. 

The German side wishes to duplicate the U.S. 
decline of cardiovascular disease and has initiated a 
national program modeled on the U.S. National High 
Blood Pressure Education Program. A risk factor 
intervention study also is being planned. Pilot studies 
are under way to gather the necessary epidemiological 
background data and to clarify the methodological 
approaches most suitable for use in the FRG. 

A Joint U.S. -FRG Workshop on Multiple Risk 
Factor Intervention Trials was held in Heidelberg in 
April 1981, where the following topics were addressed: 
Concepts of Intervention in Unselected Populations; 
Concepts of Evaluation for Cardiovascular Interven- 
tion; Elements of Hypertension Programs; and Recom- 
mendations for German-American Cooperation. At a 



colloquium following the workshop, the U.S. delegates' 
experiences with community-based cardiovascular dis- 
ease prevention programs were presented. A second 
workshop in Munich focused on epidemiology and 
preventive medicine and hypertension control in 
community-based prevention programs. During joint 
scientific and health policy discussions held in Heidel- 
berg, Bonn, Munich, and Berlin, it was decided to 
consider cooperative activities in the following areas 
during the next two years: 

•International comparable surveillance and monitoring 
of cardiovascular morbidity and mortality and their 
association with risk factors and health practices. 
•Development and exchange of techniques and 
strategies for intervention studies. 
•Development and exchange of techniques for evalua- 
tion and validation of approaches to intervention. 

A U.S. scientist visited the FRG in 1981 for joint 
discussions of the planned Multi-Center Intervention 
Trial and the health information survey that is needed 
to provide background information for the main study. 
An FRG delegation visited the U.S.A. in October 1981 to 
discuss detailed methodology and resolve specific 
problems that may arise during the survey. 

Greece 

An Agreement between the Government of the United 
States of America and the Government of the Hellenic 
Republic for Cooperation in the Economic, Scientific 
and Technological, and Educational and Cultural Fields 
was signed in April 1980. Preliminary exchanges of 
information in the area of the hemoglobinopathies have 
taken place under this agreement. The NHLBI has had 
informal cooperative activities with Greek scientists for 
many years. These involve the epidemiology of ather- 
osclerosis and the hemoglobinopathies, particularly 
thalassemia (Cooley's Anemia). 

Hungary 

Science and Technology Agreement between the 
Hungarian People's Republic and the Government of 
the United States of America on Cooperation in 
Culture, Education, Science, and Technology was 
renewed in December 1981. Article II of the Agreement 
calls for exchange and cooperation in fields of pure and 
applied science as well as technology on the basis of 
mutual benefit and common interest. The Hungarian 
Deputy Minister of Health visited the NHLBI in 1980 to 
continue exchange of information and plan cooperative 
activities in the cardiovascular area. During 1981, the 
Deputy Director, NHLBI visited the Hungarian Insti- 
tute for Cardiology to continue this planning process. 
Plans are under way for exchanges of scientists for joint 
work. 

Israel 

In January 1980, the United States Department of 
Health and Human Services and the Israeli Ministry of 
Health signed a formal 5-year agreement for Coopera- 
tion in the Field of Health. Efforts are under way to 
develop further cooperative activities in areas related to 
the Institute's mission. 



41 



Cooperative epidemiological research with Israel to 
study determinants of cardiovascular disease has been 
funded by NHLBI grants and contracts for several 
years. 

The population of Israel provides unique opportu- 
nities for epidemiological research. Jews have migrated 
there from many countries, and their diversity of 
lifestyles and genetic backgrounds constitutes a unique 
"population laboratory." Studies show that immigrants 
from different parts of the world have different plasma 
lipid distributions as well as variations in incidence and 
mortality of cardiovascular and other diseases. Euro- 
pean immigrants came in the late 1940's, Yemenite Jews 
from Yemen, Iraq, Turkey, Iran, and Syria in the 
mid-1950's, and North African Jews in the mid-1960's. 
There is continual migration of Jews with a European 
background from North and South America and the 
U.S.S.R. While 90 percent of the youth are Israeli-born, 
only 20 percent of their parents were born there. 

A multiethnic prevalence study, which is part of 
the Prevalence Study of the LRC program, is under way 
at the Jerusalem Lipid Research Clinic (LRC). All LRC 
clinics (nine in the U.S.A., one in Canada, one in Israel, 
and two in the U.S.S.R.) follow a standardized protocol. 
The aim of this network of clinics is to foster better 
diagnosis, management, and research in the area of 
hyperlipoproteinemias. The Israeli component of the 
Prevalence Study capitalizes on Jerusalem's unique 
population resource. Fifty-five countries of origin are 
represented in the Jerusalem study. This diverse 
population is divided into four broad groups according 
to country of origin (Israeli, Asian, North African, 
European/American). During 1980, the intake and 
screening of 8,609 17-year-olds was completed. Also, 
6,984 of their male parents have been screened. 

Preliminary results show important differences in 
dietary fat intake and blood lipid profiles which can be 
correlated with the country of paternal origin. Mean 
plasma high-density lipoprotein (HDL) cholesterol 
levels were highest among youths with fathers of 
European and American origin and lowest in those of 
Asian and North African descent. Second-generation 
Israelis ranked between the two groups. Total 
cholesterol levels were lowest in teenagers of North 
African descent, highest in youths of European and 
Israeli origin, and intermediate in those from Asia. 
Triglyceride levels were lowest among North Africans, 
but Asian and Israeli groups had higher values than the 
Europeans. Thus, patterns of lipid and lipoprotein 
levels previously observed in adult immigrants persist 
into a generation of native-born Israelis. Although 
ischemic heart disease incidence and mortality in Israeli 
ethnic groups correlated well with group mean total 
cholesterol values, the expected negative correlation 
with HDL cholesterol was not evident in the Asian and 
North African groups, which had the lowest HDL levels 
as well as the lowest incidence and mortality from heart 
disease. 

The study also provides clues about the relative 
roles of genetic makeup and lifestyles in the etiology of 
cardiovascular disease. On first arriving, the Yemenites 
were thin and small in stature; they had no heart disease 



or diabetes. After a single generation on an Israeli diet, 
however, they started to develop heart disease and 
diabetes but not to the extent of Israelis of European 
parentage. Another ethnic group, the Bedouin tribe, 
native to Israel, showed little or no cardiovascular 
disease, and men aged 60, 70, or 80 years had arteries 
similar to European children aged 3 to 4 years. This 
study is producing additional comparative data on 
national diets in the U.S.A. and Israel. The results of 
such strictly controlled international investigations can 
provide important clues as to whether lowering of 
blood cholesterol levels decreases heart attacks. A 
positive correlation could lead to the saving of many 
lives; a negative correlation could spare society the 
expense and social hardship of cholesterol-lowering 
diets and drugs. Medical information originating from 
the LRC international investigations will profoundly 
affect millions of lives in this and future generations. 

The NHLBI also supports a joint American-Israeli 
Migrant Study of same-sex siblings, one of whom 
migrated to Israel and the other of whom remained in 
the U.S.A. Approximately 2,400 Israelis and 1,525 
North Americans were given a complete physical 
examination to assess if differences in cardiovascular 
risk factors are influenced by genetic and/or environ- 
mental influences. Data analysis of this completed 
study is under way, and published reports are expected 
during FY 1982. 

Italy 

U.S. -Italian cooperation in the cardiovascular area was 
initiated in 1978 under the Joint U.S. -Italy Memoran- 
dum of Understanding signed by the Secretary, DHEW, 
and the Italian Minister of Health in Rome in November 
1977. The purpose of these joint activities is to 
exchange, review, evaluate, and compare U.S. and 
Italian information in specific scientific areas judged to 
be of strong mutual interest and benefit and to develop 
scientist-to-scientist exchanges in these areas. 

Three joint symposia have been held under the 
agreement. The proceedings of the first two have been 
published, and the third in in press. 

Symposia on "Measurement and Control of Car- 
diovascular Risk Factors" and "Prostaglandins and 
Cardiovascular Disease" were held in 1978 and 1979. 
The methodology used for research on prostaglandins 
and cardiovascular diseases was examined, and the 
need was established for a better understanding of the 
role of prostaglandins in the normal functioning of the 
cardiovascular system and their possible involvement 
in certain disease states. Also, the mechanism of action 
of certain drugs requiring the presence of prostaglan- 
dins needs clarification, as do derivatives that may be 
potentially useful drugs. 

A Joint U.S. -Italy Working Meeting on Methodolo- 
gy and Training in Prostaglandin Research in the 
Cardiovascular Area was held in May 1980. Problems 
were defined and common goals reviewed. The follow- 
ing three recommendations resulted: fullest support 
should be given to assay-method training programs 
which are broadly based and fully integrated, and these 
programs should be recognized as the principal areas 



42 



for exchange; deuterated standards of prostaglandins 
for gas chromatography and mass spectrometry should 
be made available at the national level, and to facilitate 
radioimmunoassay, the fullest characterization of anti- 
bodies and definition of their fields of application 
should be carried out; a working meeting should be 
held in 1982 to assess the results of joint U.S. -Italian 
efforts in this field. 

The third joint symposium, "Nutrition and Car- 
diovascular Disease," held in December 1980, explored 
in depth the scientific questions relating to the role of 
nutrition in the development and prevention of car- 
diovascular disease. A wide range of subjects was 
considered. A major topic of the symposium was the 
role of nutrition in hypertension and its control. The 
U.S. -Italy Joint Steering Committee met in conjunction 
with the symposium. It reported that cooperative 
efforts were proceeding as planned and progress was 
good. The Fourth U.S. -Italy Joint Symposium, 
"Methods of Noninvasive Diagnosis in Cardiovascular 
Disease," to be held in the U.S.A. in November 1981, 
was planned. Topics to be discussed include: character- 
istics of atherosclerotic lesions as they pertain to 
noninvasive techniques; status of the technology and 
future trends; and validation of noninvasive techniques 
and the clinical applications of these techniques. 

The first Fellow under the U.S. -Italy agreement 
worked for 3 months in the U.S.A. on the role of 
thromboxane in atherogenesis. She visited several U.S. 
laboratories to discuss work on platelet clotting, 
thromboxane, and atherogenesis. Cooperative research 
on platelets and sera from Tangier patients, who have a 
very rare genetic blood lipid abnormality, is under way. 
Platelet function testing will be carried out in Italy using 
the Fellow's unique assay system. 

Joint studies are in progress to explore alternative 
methods to prevent and treat Hyaline Membrane 
Disease (HMD) and Adult Respiratory Distress Syn- 
drome (ARDS). Pulmonary ventilation can be reduced 
or totally eliminated by using an extracorporeal mem- 
brane lung to remove metabolic carbon dioxide and 
using "apneic oxygenation" to deliver the oxygen 
necessary directly via the resting lung. NHLBI and 
Italian researchers are clinically testing a spiral blood 
coil gas exchanger on ARDS patients and on an animal 
model at high risk of developing HMD. During 1981, 
these researchers demonstrated that ARDS patients 
who met the criteria of 90 percent mortality can be 
placed on extracorporeal bypass for up to 2 days, 
allowing their lungs to heal sufficiently so that they can 
again breathe spontaneously. Similarly, when prema- 
ture lambs which normally develop hyaline membrane 
disease are placed on this system for 2 to 6 hours 
postdelivery, they do not develop the disease. After this 
time, the lambs could be taken off the respiratory assist 
system, and their lung development proceeded normal- 
ly. Collaboration with Italian researchers made human 
evaluation of this unique life-saving technique possible. 

Japan 

A U.S. -Japan Agreement in Science and Technology in 
Non-Energy Areas was signed in 1980 by the President 



of the United States and the Prime Minister of Japan. 
The agreement, which includes collaboration in the area 
of cardiovascular diseases, is the result of a long and 
successful history of cooperative research between the 
two countries. A Japanese Coordinator for the car- 
diovascular area was appointed in 1981. Information 
exchange is under way, and specific themes and plans 
for the cooperation are in the developmental stage. 
U.S. -Japanese research on nutritional control of hyper- 
tension and its sequelae has been ongoing informally 
for more than 10 years, and both sides are interested in 
expanding these studies under the formal agreement. 
Other ongoing joint research involves studies on the 
comparative rates of coronary heart disease and stroke 
and genetic, nutritional, environmental, and other 
factors which account for differences in the health 
status of U.S. and Japanese populations. 

Japanese scientists have made important contribu- 
tions to the development of animal models for the study 
of hypertension. The development of the spontaneous- 
ly hypertensive rat (SHR) at Kyoto University, and its 
use in animal research at the National Institutes of 
Health since 1969, led to ongoing collaboration between 
NHLBI intramural scientists and Japanese researchers. 
Significant differences in neurotransmitter metabolism 
were observed in these geneticallv hypertensive rats. In 
1974, a substrain of the SHR, the stroke-prone SHR or 
SHR-SP, was developed in Japan. This substrain, which 
exhibits more severe hypertension than the SHR, was 
subsequently introduced into the NIH animal colonies. 
Extensive cooperative research, using these animal 
models of hypertension and stroke, has led to signifi- 
cant discoveries on the neuronal regulation of blood 
pressure, vascular structure, and the dietary factors that 
may influence the incidence of stroke in the SHR-SP. 

SHR-SP animals fed the standard NIH rat diet had a 
considerably lower incidence of stroke than rats of the 
same strain fed the standard Japanese diet. Thus, 
SHR-SP receiving the Japanese diet evidenced more 
than 60-percent incidence of severe stroke by 10 months 
of age, whereas those receiving the NIH rat diet, though 
they developed hypertension, had only a 10-percent 
incidence of stroke. The major difference in the diets 
was the higher protein content of the NIH diet. It 
appears that the "stroke protection" is due to an 
increased intake of certain sulphur-containing amino 
acids and certain aromatic amino acids. To be effective, 
the dietary intervention must occur from the third 
through the sixth month of the rat's life (a period 
approximately equivalent to 15 to 20 years of age in 
man). Recent human epidemiological studies in Japan 
have confirmed the importance of dietarv protein in the 
development of stroke. Other studies in the SHR-SP 
rats and in Japanese men have shown the importance of 
sodium/potassium (Na/K) ratio in the diet in the 
development of hypertension. Further studies are 
ongoing in man on the nutritional modulation of 
hypertension induced by high sodium intake. Also, the 
Japanese are testing a nutritional supplement rich in 
potassium chloride for use in borderline hypertensives. 
Japanese and U.S. workers have developed predictive 
tests for hypertension using red blood cell (RBC) 



43 



membrane properties. In young SHR's which have not 
yet developed hypertension, the RBC's show an 
increased permeability to sodium ions, lipophilic ions, 
and an increased osmotic fragility. Joint experiments 
are continuing to establish whether RBC membrane 
properties can provide an indicator of human suscepti- 
bility to hypertension before overt high blood pressure 
develops. 

A joint publication on the nutritional prevention of 
stroke has been submitted for publication, and a joint 
project, Experimental Studies and Dietary Prevention of 
Hypertension and Atherosclerotic Diseases, is under way at 
NHLBI and in Japan. It is funded cooperatively by the 
National Science Foundation and the Japanese Society 
for Promotion of Science for 2 years (1981 and 1982). The 
Japanese workers have now also developed an arterio- 
lipodosis-prone rat (ALR) which provides a good model 
for studying atherosclerosis. 

It is anticipated that the cooperative agreement 
between the U.S.A. and Japan will facilitate these 
important research efforts in hypertension and insure 
that scientifically validated results will be applied 
rapidly to the prevention, diagnosis, and treatment of 
hypertension, stroke, kidney failure, and atheroscler- 
osis. 

The Honolulu Heart Program, a long-term prospec- 
tive study of coronary heart disease and stroke in 8,006 
men of Japanese ancestry living in Hawaii, was started 
in 1970. The 10-year disease incidence and mortality 
roster has now been completed. Heart disease and 
mortality in this population were intermediate between 
the high levels of heart disease found in a similar cohort 
living on the U.S. mainland and the lower levels of one 
living in Japan. However, stroke prevalence was three 
times as great in the indigenous Japanese cohort than in 
the Honolulu cohort. There was a strong negative 
correlation between cancer, particularly colon cancer, 
and serum cholesterol levels in the Japanese cohort. The 
10-year re-examination of 2,000 of these men is now 
under way and will be completed during 1982. The risk 
factors, both positive and negative, underlying these 
changes in morbidity and mortality trends are currently 
under study. 

Kuwait 

The United States-Kuwait Technical Cooperation Pro- 
gram in Health was signed May 1981. In March 1981, 
the Director, Kuwait National Health Planning Office, 
visited the NHLBI to explore programs in the preven- 
tion of cardiovascular disease. Kuwait is developing a 
National Health Plan and under the agreement is 
seeking consultant help to develop a National High 
Blood Pressure Education program. Like the U.S.A., 
Kuwait's major health problems are hypertension, 
cardiovascular disease, accidents, and other chronic 
diseases. 

Nigeria 

An Agreement for U.S. -Nigeria Cooperation in Biome- 
dical Research was signed in September 1981 as a 
followup to the NIH-Nigerian Task Force meeting held 
earlier in that year. Nigeria shares with the U.S.A. such 



chronic health problems as cardiovascular diseases and 
cancer. As the country undergoes major socioeconomic 
changes, these diseases are becoming more prevalent. 
Cooperative activities with the NHLBI are planned in 
the area of cardiovascular diseases, with special empha- 
sis on hypertension and in the hemoglobinopathies, 
especially sickle cell anemia. Individual U.S. and 
Nigerian scientists are already undertaking research in 
epidemiology and hypertension control, and it is 
anticipated that these efforts will increase as lines of 
scientific communication continue to develop and 
strengthen between the two countries. 

Senior scientists from several African countries 
(Sudan, Tanzania, Nigeria) who visited the NHLBI 
during FY 1981 showed a growing interest in carrying 
out cooperative projects in the area of hypertension. 
This disease is a common problem to the U.S. and 
African black populations. In the U.S.A., the disease is 
more prevalent and more severe among blacks. Hyper- 
tension appears to present different sequelae among 
the African black population, where there are fewer 
heart attacks and strokes associated with the disease 
than in the U.S.A. African hypertensives die more often 
from renal disease or cardiac failure. Furthermore, 
hypertension and other cardiovascular diseases such as 
rheumatic heart disease occur in a more telescoped 
timeframe in Nigeria than in the U.S. This provides a 
unique opportunity for joint studies to be done in a 
shorter timeframe than would be possible in the U.S.A. 
During FY 1981, several senior African scientists 
worked for extended periods in the United States to 
carry out hypertension-related research. 

People's Republic of China (PRO 

An agreement between the Government of the United 
States of America and the Government of the People's 
Republic of China on Cooperation in Science and 
Technology was signed in January 1979. The subse- 
quent U.S.-PRC Protocol for Cooperation in the Science 
and Technology of Medicine and Public Health in June 
1979 identified cardiovascular disease as one of the 
seven areas of cooperation. 

During 1979, the PRC coordinator visited the 
NHLBI for preliminary discussions. The Director, 
NHLBI, headed a five-member U.S. delegation for a 
reciprocal visit to the PRC in 1980. As a result, a 
proposed plan for U.S.-PRC Cooperation in the Car- 
diovascular Area was signed by the coordinators and 
approved by the respective governments. It was 
reported to the Joint Committee that "the U.S. and PRC 
sides have determined that one area, cardiovascular 
epidemiology, is by far the area of greatest mutual 
interest, mutual need, and mutual benefit to the 
peoples of both countries at this time." 

The Chinese Coordinator for the Cardiovascular 
Area and the new Director for the National Car- 
diovascular Institute and FuWai Hospital in Beijing and 
three additional Chinese specialists visited in the 
United States in March 1981. A U.S.-PRC Joint Work- 
shop on Arteriosclerosis and Hypertension was held, 
and plans for future cooperative activities were formu- 
lated. A four-member U.S. working group of car- 



44 



diovascular specialists visited China in April 1981 to 
initiate joint discussions of the planned U.S.-PRC 
studies of epidemiology of cardiovascular disease and 
the risk factors important in developing such disease. 
U.S. and Chinese scientists formulated a proposed joint 
U.S.-PRC protocol and discussed the standardization 
measurement techniques, collection of data, and analy- 
sis of joint data. It is anticipated that a final joint 
protocol will be presented to the U.S.-PRC Joint Health 
Committee at its Third Meeting in April 1982 in 
Washington. 

In March 1981, two Chinese fellows commenced 
12-month exchange visits to the U.S.A. to carry out joint 
research on the biochemistry of atherosclerosis and 
cellular studies of human atherosclerosis. Exchanges of 
information and scientists in the scientific areas desig- 
nated for cooperation are expected to continue. 

Poland 

Exchange activities continued under the 1974 U.S.- 
Polish Agreement for Health Cooperation between the 
Department of Health and Human Services and the 
Ministry of Health and Social Welfare of the Polish 
People's Republic. A Joint Summary of Discussion was 
signed in March 1981 by the Director for Research 
Coordination of the National Institute of Cardiology, 
Warsaw, and the Director, National Heart, Lung, and 
Blood Institute, following a U.S. -Polish Symposium on 
Ischemic Heart Disease. The symposium covered a 
wide range of topics including: Epidemiology of 
Ischemic Heart Disease; Role of Prostaglandins in 
Ischemic Heart Disease; Prostacyclin and Atheroscler- 
osis; Surgical Management of Ischemic Heart Disease; 
Noninvasive Diagnostic Techniques for Cardiovascular 
Disease; Technical Aspects of Endomyocardial Biopsy 
and its Value in Diagnosis of Cardiomyopathy; and 
Rehabilitation Following Acute Myocardial Infarction 
including the Psychological Indices of the Rehabilita- 
tion Process. 

At a Colloquium on the Epidemiology of Car- 
diovascular Disease held in conjunction with the joint 
symposium, data were presented on cardiovascular 
mortality trends in the U.S.A. and Poland. The results 
of the pilot study for the U.S. -Poland Joint Study of the 
Prevalence of Lipid Metabolism Disturbances were also 
evaluated. 

Simultaneously, a U.S. -Poland Steering Commit- 
tee meeting took place to review activities carried out 
under the three areas previously agreed upon. 

Area A. — Basic Research in Etiological Mechanisms. A 
U.S. scientist worked in Cracow for 2 months carrying 
out joint experiments on the endogenous production of 
Prostaglandin - GI2 and its metabolites. A Polish expert 
spent 2 months in the U.S.A. working in advanced 
lipoprotein research. He learned the latest U.S. tech- 
niques and commenced studies on apolipoproteins, 
which he is continuing in Poland. 

Area B. — Clinical Research. A Polish physician 
worked in the U.S.A. on the diagnosis and treatment of 
cardiomyopathy and isotopic procedures for evaluating 
heart hemodynamics. A reciprocal visit to Poland by a 
U.S. physician is planned to carry out research on 



noninvasive techniques in cardiovascular diagnosis and 
to learn endomyocardial biopsy techniques that have 
been successfully employed in Poland for the diagnosis 
of cardiomyopathy. A protocol for a collaborative study 
on the diagnosis and treatment of cardiomyopathy is 
under development. 

Area C. — Epidemiological Research. A cooperative 
study, The Cardiovascular and Clinical Correlations of 
High Density Lipoproteins (HDL), is under develop- 
ment to explore the reasons for the marked differences 
in cardiovascular disease and risk factor trends in the 
U.S.A. and Poland. Cardiovascular death rates in the 
U.S.A. have decreased sharply, whereas these rates 
have increased in Poland. A Polish scientist visited the 
U.S. Lipid Research Clinics (LRC) to learn LRC 
techniques and procedures to be used in the joint study. 
A U.S. clinical chemist worked at the Departments of 
Metabolic Disease and Clinical Chemistry of the 
Institute of Medicine, Academy of Medicine, Cracow, 
to help initiate U.S. LRC procedures for blood cholester- 
ol and triglyceride determinations. Standards, frozen 
sera, and quality control materials were supplied to the 
Polish side for use in the joint studies, allowing the 
Cracow laboratory to be standardized according to LRC 
procedures. In FY 1981, a U.S. epidemiologist and a 
biostatistician reviewed progress of the screening teams 
in Warsaw and Cracow. A small working group met to 
develop a protocol for a collaborative U.S. -Poland 
Study of Ischemic Heart Disease which would produce 
comparable valid data in the U.S.A. and Poland. The 
planned study will determine the prevalence of risk 
factors, ischemic heart disease, and risk of ischemic 
heart disease morbidity and mortality in middle-aged 
men comprising a subset of the Polish population 
selected from a planned WHO study. 

A U.S. scientist visited Poland for joint review of 
the 3-year results of the Polish Trial in Multifactorial 
Prevention of Coronary Heart Disease. This trial, 
conducted under the U.S. -Polish Agreement, is part of 
a larger European study under WHO auspices. The 
study design calls for random allocation of pairs of 
factories for either intervention or control. The study 
population consists of 11 intervention factories with 
9,115 subjects and 11 control factories with 8,120 
subjects. Baseline findings from cardiovascular screen- 
ing of 8,045 men in the intervention factories and 713 
men (a 10-percent sample of the control group) have 
been published, as has a joint publication of recruitment 
data and initial findings from the Polish trial. The data 
are compared to those obtained in the United Kingdom, 
Belgium, Italy, and Spain. The Belgian study popula- 
tion was at highest risk of CHD; the Polish men, at 
lowest risk. Analysis of 3-year mortality data is under 
way from 6,000 men whose individual dietary intake 
data were recorded earlier. These dietary data will be 
analyzed for relationships to coronary heart disease and 
malignant neoplasms by a Polish mathematician who 
received 4 weeks of advanced statistical training at the 
Center for Disease Control plus an additional two 
weeks of training at the NHLBI. 

Under the U.S. -Poland Collaborative Research 
Agreement, supported by the Marie Sklodowska-Curie 



45 



Fund, a Follow-up Study of Chronic Non-specific 
Respiratory Disease in Cracow continues. During FY 
1981, two U.S. scientists visited Warsaw and Cracow to 
review progress. This study was first initiated in FY 
1968, and 4,800 individuals (a randomized sample) from 
the Cracow population were studied. During 1973, 
4,400 of the original study population were re- 
examined, and during 1981, approximately 3,500 of 
these individuals were re-examined for a third time. 
Standardized interviews and a medical exam which 
included lung function testing, sputum analysis, age, 
weight, and height measurements were carried out. 
This 13-year prospective study will yield important new 
scientific data on risk factors affecting the incidence, 
prevalence, and persistence of chronic nonspecific 
respiratory disease. No U.S. study of such duration 
exists, and it should supply further explanations of the 
natural history of this disease. 

United Kingdom 

Scientists from the NHLBI Division of Intramural 
Research continued their cooperation with British 
investigators in the development of a computer-based 
chemical information system (CIS). While the manage- 
ment for the CIS continues to be located in the NHLBI, 
funding during FY 1981 was drawn largely from the 
NIH management fund. The system includes analytical 
programs to accomplish iterative analysis of complex 
nuclear magnetic resonance (NMR) spectra, or general 
curve-fitting linear regression analysis, mathematical 
modeling, chemical synthesis programs, and many 
other specialized data bases. Utilizing joint efforts, the 
data bases for the system were assembled by the 
National Institutes of Health, the Mass Spectrometry 
Data Center (within the Department of Industry of the 
British Government), the Environmental Protection 
Agency, the National Bureau of Standards, and several 
other U.S. Government agencies as well as nongovern- 
ment U.S. units and groups from other nations. This 
valuable information system, which contains 30 special- 
ized data bases, is being made available to scientists in 
North America and Europe by means of an internation- 
al teleprocessing network. During FY 1981, 14 countries 
cooperated in the further development of the CIS: 
Australia, Finland, France, Germany, Holland, Hun- 
gary, Japan, Poland, Sweden, Switzerland, United 
Kingdom, the U.S.S.R., and Yugoslavia. 

The British Norwegian Migrant Study surveyed by 
mail 73,884 men and women in the United States, 
Britain, and Norway to attain the prevalence of 
"angina" and other cardiorespiratory symptoms. The 
symptom of "angina" was reported more frequently by 
persons remaining in Britain and Norway than by the 
migrants to the U.S.A. During a 5-year period following 
the survey, angina was found to be a strong predictor of 
cardiovascular mortality. In the absence of angina, the 
migrants had a mortality rate similar to that of 
nonmigrants, regardless of country of origin. However, 
the British had higher mortality rates from cardiovascu- 
lar and noncardiovascular causes than the Norwegians. 
The primary determinant of angina prevalence was 
found to be migration status. It is believed that those 



who migrated constituted a healthier group than those 
who did not migrate. 

The United Kingdom is one of the five countries 
undertaking the European Trial in Multifactorial Preven- 
tion of Coronary Heart Disease. The other countries, which 
use a common protocol and pool their data, are 
Belgium, Italy, Poland, and Spain. The United King- 
dom study contains 24 factories with random allocation 
of pairs of factories to either a 6-year period of 
intervention efforts on risk factors or to control 
monitoring and followup of morbidity. Final enroll- 
ment was completed for all countries in 1977. The 
combined study consists of 63,732 men aged 40 to 59 
years at entry and represents 88 factories. Followup is 
complete for the United Kingdom, Belgium, and Italy, 
and results are being published. Intervention achieved 
modest reduction of risk factors overall, and more 
substantial reductions were obtained in men at high 
risk. 



U.S.S.R. 

During FY 1981, cooperation between the National 
Heart, Lung, and Blood Institute and the U.S.S.R. 
Ministry of Health continued under the bilateral health 
agreement signed in 1972 and renewed in 1977 by the 
U.S. Secretary of State and the U.S.S.R. Minister of 
Health. Cooperation is proceeding in seven areas: 
Arteriosclerosis; Ischemic Heart Disease; Myocardial 
Metabolism; Congenital Heart Disease; Sudden Cardiac 
Death; Blood Transfusion, Blood Components, and 
Hepatitis; and Hypertension. Activities in these areas of 
joint cardiovascular research provide a constructive 
forum for interaction on problems of major national 
interest and need. The cooperative relationships estab- 
lished under this exchange provide a foundation of 
mutual respect and rapport which continues to yield 
scientific results of mutual benefit. 

During the 9 years of cooperation, 502 specialists 
were exchanged in the seven cardiovascular areas for a 
total of 353 person-months. More than 100 U.S. and 
Soviet institutions have participated in the exchange, 
more than 60 in the U.S.A. and 40 in the U.S.S.R. 
Nineteen joint symposia have been held, and the 
proceedings have been published (or are being pre- 
pared for publication) in both English and Russian. 
Nearly 600 scientific reports, abstracts, and related 
articles have been published under the aegis of the 
exchange. 

Area 1, Pathogenesis of Arteriosclerosis -The U.S.- 
U.S.S.R. collaboration in Area 1 provides a unique 
opportunity to study and compare the determinants 
and sequelae of coronary heart disease in different 
epidemiological settings. Both countries show a high 
incidence of heart disease, but differ significantly in 
ethnic and environmental characteristics. The highlight 
of cooperation during fiscal year 1981 was the First Joint 
U.S. -U.S.S.R. Lipoprotein Symposium held in Leningrad 
in May 1981. Presentations reported the results of 7 
years of joint laboratory work and epidemiological 
studies on the prevalence of hyperlipoproteinemia and 
ischemic heart disease in Soviet and American popula- 
tions. Further data were reported on correlates of 



46 



high-density lipoprotein (HDL) cholesterol. High levels 
of HDL cholesterol are associated with longevity, and 
this factor has been shown to be higher in Soviet 
populations than in comparative sample U.S. popula- 
tions. Discussions focused on developing a basis for 
further U.S.-U.S.S.R. joint studies designed to explain 
the differences in HDL cholesterol levels among lipid 
research clinic (LRC) populations in the two countries, 
and to explore the potential for favorable modification 
of HDL cholesterol in populations. The cultural diversi- 
ty of the studies, and the strong emphasis on the use of 
common procedures to collect data of comparable 
quality, increase the importance of the data and their 
ability to add to our understanding of heart disease. 

One report, using multiple regression analyses, 
showed that in U.S. populations, 17 percent of HDL 
cholesterol could be statistically explained by behavior- 
al characteristics, including alcohol intake and physical 
activity. The U.S. report corroborates conclusions of 
others that abstinence from cigarette smoking, a lean 
body, physical exercise, and moderate alcohol con- 
sumption are associated with increased level of HDL 
cholesterol, a condition regarded to be antiatherogenic. 
However, it is premature to infer a causal relationship 
between the above factors and HDL cholesterol levels. 
Proof of causality has to be reserved for future clinical 
and experimental studies. Nevertheless, the findings 
reported suggest the potential for favorable modifica- 
tion of population HDL cholesterol levels by hygienic 
means such as diet, exercise, and abstinence from 
cigarette smoking. 

Papers also outlined the salient characteristics of 
the collaborative U.S.-U.S.S.R. study of the prevalence 
of dyslipoproteinemias, including an overview of the 
structure of the study, characteristics of the populations 
studied, and the common procedures utilized, such as 
plasma lipids and lipoprotein cholesterol determina- 
tions, as well as nutritional intake assessment and 
resting electrocardiography studies. 

Comparisons of prevalence of ECG abnormalities 
and angina in comparative U.S. and U.S.S.R. male 
populations revealed that in both countries, the preva- 
lence of ECG abnormalities and angina is higher for the 
50- to 59-year age group than the 40- to 49-year age 
group. Also, the prevalence of angina is 3.3 times 
higher in the older groups compared to the younger 
groups. In both countries, people with ischemic heart 
disease had higher levels of total plasma cholesterol, 
triglyceride, LDL cholesterol, and systolic and diastolic 
blood pressure. Some of the differences may be related 
to the industrial location of the U.S.S.R. populations 
studied. The U.S. studies came from a variety of 
locations ranging from large cities to small rural towns. 

In general, in the selected sample populations in 
both countries, the levels of plasma cholesterol and 
triglycerides are high. This is typical of developed 
countries with a high prevalence of ischemic heart 
disease. The analyses, based on common survey 
methods and highly standardized laboratory measure- 
ments, provide interesting contrasts in population 
distributions of lipids and lipoproteins in U.S. and 
U.S.S.R. middle-aged men. The implications of these 



analyses are that plasma total cholesterol and HDL 
cholesterol levels are significantly higher, and tri- 
glyceride levels are significantly lower in the U.S.S.R. 
than in the U.S.A. Some of the differences observed in 
the distributions of these lipids and lipoprotein frac- 
tions may be attributable to environmental factors; 
some are likely to be attributable to genetic factors. The 
findings of distributional differences reinforce the 
importance of studying the relationship of these 
differences to various coronary heart disease risk factors 
and to the disease itself. 

The above results represent the culmination of 
ongoing efforts by both sides to maintain good 
communication throughout the collaborative process, 
particularly through exchanges of individual scientists 
and working groups. A joint U.S.-U.S.S.R. Working 
Group meeting was held in conjunction with the 
symposium to discuss problems and review techniques 
to ensure the comparability of data gathered for the 
joint study. In Moscow, the working group reviewed 
the Followup Study and Prevalence Study data collec- 
tion procedures and visited the ECG laboratory to 
observe ongoing exercise testing. In Leningrad, proce- 
dures in connection with the prevalence study were 
reviewed, and mortality classification procedures were 
discussed. 

A Joint U.S.-U.S.S.R. Steering Committee meeting 
in Area 1 was held in conjunction with the symposium 
to review progress and develop plans for further 
activities. Both sides agreed to continue the exchange of 
epidemiologists and biochemists for individual studies 
and collaborative analysis of prevalence study data. 
Two areas were suggested for further data analysis and 
scientific publications: clinical chemistry data and blood 
pressure analysis. Plans are under way to gradually 
increase the proportion of basic research within Area 1. 
This is being initiated in parallel with the anticipated 
completion of the analysis phase of the epidemiological 
studies. Three basic research areas have been jointly 
agreed upon for continued collaborative work: cellular 
and lipid interactions at the arterial wall; structure and 
properties of lipoproteins; and platelets and lipopro- 
teins. 

Area 2, Management of Ischemic Heart Disease -During 
fiscal year 1981, joint cooperation in Area 2 focused on 
the Second Joint U.S.-U.S.S.R. Symposium on Ischemic 
Heart Disease held in Seattle, Washington, on March 20, 
1981. Presentations at the symposium reported on 
patient-oriented research to find ways to minimize the 
mortality, morbidity, and suffering resulting from 
advanced coronary heart disease, including the results 
of ongoing studies in each country comparing different 
approaches to medical and surgical treatment of this 
disease. 

One study reported on the use of ECG exercise 
testing in evaluating patients with ischemic heart 
disease. The results indicate that the ability of stress 
testing to predict coronary artery disease is limited in a 
heterogenous population in which the prevalence of 
disease is estimated through classification of chest pain 
and the sex of the patient. However, probability curves 
derived from sophisticated statistical analysis on tread- 



47 



mill and angiographic data demonstrated that exercise 
testing provides more diagnostic information than 
clinical data alone in patients with definite and probable 
angina. Exercise testing in men with nonspecific chest 
pain was of limited value since disease prevalence was 
already low. 

Another presentation reported on the procedure 
and results of an NIH consensus development confer- 
ence on coronary artery bypass surgery. Evidence 
shows that an improvement in the quality of life, a 
decrease in myocardial ischemia, and an increase in 
survival have been demonstrated after coronary artery 
bypass in selected subsets of patients. Data presented at 
the symposium also indicate that coronary artery 
bypass surgery prolongs life in most patients with left 
main coronary artery (IMCA) disease, particularly those 
with severe IMCA narrowing or severe left ventricular 
dysfunction. However, subgroups of IMCA patients 
who fare well with medical treatment alone are 
identifiable. These results and others were discussed by 
the seven-member Soviet delegation and nine-member 
U.S. delegation participating in the symposium. The 
proceedings are being prepared for publication. 

In conjunction with the symposium, a joint 
U.S.-U.S.S.R. working meeting was held to discuss the 
comparability of data in the joint clinical study to 
systematically assess and compare, in a well-defined 
group of cardiac patients, the relative effectiveness of 
the different treatment modalities used in the two 
countries. U.S. and Soviet angiographers read ventri- 
culograms and angiograms with very good agreement 
between the independent readings. Comparisons were 
made of intake data and early survival experience. 
Subsequent to the symposium, the U.S. side received 
followup data which are being entered in the Data 
Coordinating Center in Seattle for computer analysis. 

In addition to participating in the Second Joint 
Symposium, the Soviet scientists attended the 30th 
Annual Scientific Session of the American College of 
Cardiology in San Francisco. They visited laboratories 
in Palo Alto, California, and in Birmingham, Alabama, 
where mutual interest was expressed in the following 
themes: the role of spasm in ischemic heart disease; 
circulatory insufficiency in ischemic heart disease; the 
role of thrombocytes and blood coagulation in ischemic 
heart disease; hypertensive heart disease; and issues of 
angiography. Future U.S.-U.S.S.R. cooperation will 
build on these areas of mutual interest. 

Prior to the symposium, a five-member U.S. 
delegation visited the U.S.S.R. in October 1980 to 
review progress on the joint studies, to discuss data 
analysis techniques, and to develop criteria for inter- 
pretation of results. The U.S. delegation visited labor- 
atories and scientific institutions in Moscow, Kaunas, 
Vilnius, and Tashkent. Problems of reference group 
comparability were resolved, and a schedule for 
transmission of followup data developed. 

Further plans include continued monitoring of 
patients up to June 1983. Followup data are to be 
forwarded to the Data Coordinating Center through the 
U.S. Coordinator twice a year for the third, fourth, and 
fifth years of followup; and some of the U.S.S.R. data 



are to be analyzed as both data in the reference group 
and in the intensive treatment group. Also, a joint 
working meeting is planned for 1982 in Moscow. Both 
sides acknowledged interest in further collaborative 
studies on ischemic heart disease. 

Area 3, Myocardial Metabolism -Joint cooperation 
in Area 3 incorporates a number of basic research 
projects. These are aimed at the discovery of new 
information that may help in the development of 
improved methods for prevention and treatment of 
cardiac disease. Current studies focus on the manner in 
which heart muscle cells obtain energy, regulate their 
growth, coordinate their contractions, and respond to 
alterations in their environment. Accordingly, pre- 
sentations at the Fifth Joint U.S.-U.S.S.R. Symposium on 
Myocardial Metabolism, which was held in June 1981 in 
Hershey, Pennsylvania, were organized to report the 
results of joint studies in each of the above areas. 

One symposium presentation reported on the 
results of a joint study by U.S. and U.S.S.R. scientists 
on energy channelling by heart creatine kinase, particu- 
larly the influence of oxidative phosphorylation on the 
kinetics of the reaction. The success of this highly 
specialized joint work derives from the complementary 
skills of the U.S. and U.S.S.R. cooperating scientists. 

Studies to elucidate the microprocesses involved in 
normal heart function and their modification in dam- 
aged heart muscle were also reported jointly by U.S. 
and U.S.S.R. scientists. These include studies of the 
energetics of heart muscle contraction and relaxation, 
particularly the role of cyclic nucleotides in these 
processes. Calcium transport by the cardiac sarcoplas- 
mic reticulum is being investigated to define more 
accurately the functions of this important cell compo- 
nent. Joint experiments are also under way to define the 
immunological properties of calcium ATPase of the 
cardiac and skeletal muscles. 

U.S. and U.S.S.R. scientists also reported on the 
development of new methods to evaluate the hormone 
receptor apparatus in cells. Joint studies are under way 
on the mechanisms by which glucocorticoid and 
thyroid hormones potentiate the effect of catechola- 
mines and how these hormones produce functional 
changes of the membranes surrounding the various 
intracellular organelles. 

These projects are indicative of the various 
approaches taken by cooperating scientists to investi- 
gate normal heart function as well as the disruptions of 
the biochemical and biophysical processes that result 
from a heart attack. Some effects of myocardial 
infarction are reversible; others are not. One of the 
major thrusts of research in this area is determining 
with greater precision the exact point of irreversible cell 
damage so that therapies may be designed accordingly. 

The U.S. side plans to publish the Proceedings of 
the Fifth Joint Symposium on Myocardial Metabolism 
as a supplement to an international scientific journal. 
The Soviet side will publish the proceedings in Russian. 

For the future, exchanges of scientists will continue 
for experimental work to assess and limit the extent of 
heart muscle damage following myocardial infarction, 
including studies of amino acid metabolism, protein 



48 



turnover, and nitrogen metabolism in heart muscle as 
well as joint research on new approaches for targeting 
drugs to damaged heart tissue. 

Area 4, Congenital Heart Disease- Congenital heart 
disease is an important cause of premature death and 
can significantly impair the quality of life from child- 
hood to adulthood. The objectives of U.S.-U.S.S.R. 
collaboration in Area 4 are to explore new methods of 
diagnosis and postoperative care to reduce mortality 
from congenital heart disease and to improve the 
surgical treatment of complex heart defects. Coopera- 
tion has focused primarily on the holding of joint 
symposia and exchanges of working groups, delega- 
tions, and individual surgeons and physicians. 

In followup to the Fourth Joint U.S.-U.S.S.R. 
Symposium on Congenital Heart Disease held in September 
1980 in Moscow, the U.S. and U.S.S.R. chairmen met in 
May 1981 with the NHLBI staff in Bethesda to discuss 
progress and plans in joint cooperative activities on the 
diagnosis, treatment, and surgical repair of congenital 
malformations of the cardiovascular system. As a result 
of the meeting, it was agreed that further exchanges of 
scientists would be fruitful in the following areas: the 
study of cardiac function and the blood circulation 
system utilizing mathematical models following open 
heart surgery; the study of valvular grafts in children up 
to 14 years of age; the study of possible surgical 
treatment of rare forms of cardiac arrhythmias; the 
study of severe forms of pulmonary hypertension in 
children up to age 10; and the study of emergency 
surgery for newborn infants and those in the first 3 
years of life who have congenital heart defects. 

In addition to the joint working meeting, the visit of 
the U.S.S.R. chairman and his deputy included discus- 
sions with U.S. surgeons attending the meeting of the 
American Society for Thoracic Surgery in Washington, 
D.C. Followup observations of surgery at Duke Uni- 
versity Medical Center, Durham, North Carolina, the 
University of California in San Francisco, and the 
Children's Hospital Medical Center in Boston led to the 
exchange of information on methods to insure safety 
during operations; development of new types of 
operations; prevention of complications during opera- 
tions and in the postoperative period; and program- 
ming for experimental and computer analysis of patient 
followup and treatment. 

Area 5, Sudden Death- Sudden cardiac death claims 
the life of one American every minute. It constitutes the 
leading cause of death in the U.S.A., as well as in other 
industrialized nations. In the U.S.A., 50 percent of all 
deaths from coronary heart disease occur suddenly. 
The immediate mechanism of sudden death is believed 
to be a disturbance in heart rhythm. 

The goal of scientific collaboration in Area 5 is to 
learn more about the mechanisms of arrhythmias and 
precisely how antiarrhythmic agents intervene to 
normalize the heart's electrophysiologic functions. 
Joint cooperation focuses on the pathological anatomy 
and electrophysiology which may lead to sudden 
cardiac death, and the pharmacology of possible 
prophylactic antiarrhythmic drugs. Six topics have been 
designated for scientific exchange in Area 5: pathologic- 



al anatomy, electrophysiology of sudden death; study 
of the effects of antiarrhythmic drugs; clinical aspects of 
sudden death; epidemiology of sudden death; and 
higher nervous and peripheral nervous activity in 
ventricular arrhythmias and sudden death. 

Future plans in Area 5 include a U.S.S.R. Working 
Group visit to the U.S.A. in late 1981, in anticipation of 
the Third Joint Working Symposium to be held in 1982 
in Kaunas, Lithuania. The symposium will be held in 
conjunction with the International Congress of Cardiol- 
ogy to be hosted by the Soviet Union in June. The U.S. 
delegation will be reviewing ongoing USSR studies at 
research centers in Riga, Tallin, and Leningrad. 

Area 6, Blood Transfusion -U.S. -U.S.S.R. coopera- 
tion in Area 6 is concerned with research on the 
preservation and use of blood and blood products in 
cardiovascular surgery, focusing primarily on the 
problems associated with hepatitis, posttransfusion 
hematologic complications, and blood substitutes. 
Also, in the recent past, the U.S. and U.S.S.R. Working 
Programs in Area 6 have gradually developed an 
interest in joint cooperation on thrombosis and hemo- 
stasis, with particular emphasis on hemophilia and 
other genetic bleeding disorders, and on platelet 
abnormalities. A delegation of four U.S.S.R. scientists 
visited the U.S.A. in November 1980 for discussions of 
blood-transfusion-related research, including the role 
of platelet-vascular wall interaction in homeostasis, and 
the importance of thrombin and plasmin generation in 
the disseminated intravascular blood coagulation syn- 
drome. These discussions led to an exchange of 
methodologies on blood separation and to the develop- 
ment of plans for continued cooperation. 

A five-member working group visited the Soviet 
Union in May 1981 to investigate the treatment and 
management of patients with abnormal hemostatic 
mechanisms and to examine physiologic and pathologic 
alterations of the blood-vascular system as a result of 
transfusion. In addition, proposals were discussed for 
the exchange of specialists in the areas of preservation 
of platelets and red cells, blood substitutes, the 
prevention of hepatitis, and the use of blood and blood 
products. The U.S. investigators visited scientific 
centers in Moscow and Leningrad and also the Institute 
of Hematology and Blood Transfusion in Tbilisi. Sites 
visited in Moscow included the Blood Transfusion 
Division, the Laboratories of Cryopreservation, Gra- 
vitation Surgery, Pathophysiology, and the Hemophilia 
Center in the Central Institute of Hematology and Blood 
Transfusion. As a result of joint discussions, potential 
cooperative projects were outlined in hemophilia, 
plasmapheresis, blood component preservation, and 
the mechanisms of thrombohemorraghic complications 
during massive transfusions. 

In conjunction with the working group meeting, 
two U.S. exchange scientists visited the Soviet Union to 
present lectures and conduct joint discussions with 
Soviet counterpart specialists. One of the scientists 
discussed topics in blood transfusion therapy with 
special emphasis on the application of electron micros- 
copy to the problem of platelet morphology. The other 
scientist focused on the storage of blood components 



49 



and on donor risks relative to blood separation 
technology and the use of chemical agents for the 
separation of blood components. She also presented an 
overview of the application of plasma exchange in a 
variety of medical conditions and discussed the collec- 
tion and transfusion of blood components such as 
granulocytes, platelets, and mononuclear cells. 

Plans for further collaboration include the follow- 
ing activities: continued exchanges of scientists for 
research on blood substitutes, posttransfusion hepatitis 
and plasmapheresis; development of preliminary coop- 
erative protocols for projects of mutual interest de- 
signed to allow a comparison of U.S. and U.S.S.R. 
results and data; continued exchange of reagents and 
reference preparations as may be required in jointly 
approved protocols and to compare laboratory method- 
ologies; development of joint publications on coopera- 
tive studies; exchange of delegations to monitor 
progress of collaborative activities and to review the 
status of research; and development of plans for a Third 
U.S. -U.S.S.R. Joint Symposium in Moscow, in 1983. 

Area 7, Hypertension -The Joint U.S. -U.S.S.R. Sym- 
posium on Biobehavioral and Epidemiological Aspects of 
Hypertension , held in May 1981 in Bethesda, was the 
focus for cooperative activity between U.S. and Soviet 
scientists working to learn more about the prevalence, 
causes, treatment, and prevention of this "silent killer. " 

One U.S. paper reported evidence that certain 
animals, by virtue of their genotype, exhibit unusually 
pronounced cardiovascular reactions to stressful stimu- 
li. Additionally, evidence derived from animal models 
indicates that chronic exposure to a stressful environ- 
ment can profoundly affect the ultimate level of blood 
pressure, but only in animals with a genetic predisposi- 
tion to hypertension. These data suggest that genetic 
factors must be assessed and accounted for when 
examining the importance of psychological influences 
in the pathogenesis of hypertension. 

Another paper reported on population studies of 
U.S. and U.S.S.R. individuals with categorically de- 
fined diastolic hypertension who did not have blood 
pressure levels controlled below 95mm Hg at the time of 
the studies in 1972-76. Average followup of 4 years 
duration disclosed a sizable gradient of increasing 
cardiovascular disease mortality in relation to blood 
pressure levels within the range traditionally consi- 
dered high-normal, or slightly elevated. These observa- 
tional survey findings cannot address the causal nature 
of the relationships. However, they do suggest poten- 
tial for either primary prevention or modification of 
extant elevated blood pressure by hygienic measures, 
and furthermore, suggest that a measureable impact on 
mortality might result from interventions of this type. 
They also provide justification for further collaborative 
lifestyle interventive research designed to lower mor- 
bidity and mortality, and suggest the importance of 
further developing nonpharmacological approaches to 
the prevention and treatment of hypertension. 

Reports by both sides also emphasized the need to 
know more about the role of the nervous system in 
cardiovascular disease, to gain a better understanding 
of the neural pathways that influence cardiovascular 



function. Soviet work on hypertension supports the 
view that hypertension results from changes in central 
nervous system functions produced by conflict situa- 
tions, and, among the various operations which can be 
effective in inducing these conflict states are: immobili- 
zation, constant irregular harmful stimulation, and 
significant, lengthy anticipation of harmful event. 
Where Soviet research emphasizes the search for the 
central nervous system structures involved in the 
peripheral adaptations, U.S. studies tend to focus on 
functional relationships between environmental factors 
and subsequent long-term circulatory adaptations. 

Following the symposium, a Soviet specialist 
visited U.S. scientific centers including the NHLBI, the 
National Institute on Aging in Baltimore, Maryland, 
and the Regional Primate Research Center of the 
University of Washington, Seattle, for discussions with 
U.S. scientists on the neurophysiological mechanisms 
of emotional stress in experimental animals. The 
NHLBI Chief of the Behavioral Studies Branch visited 
the Soviet Union in September 1981 for discussions of 
joint biobehavioral activities during the coming year. 

Future plans include a visit to the U.S.S.R. by a 
U.S. working group in 1982 to assess problems of 
definition and classification of hypertension; examine 
the clinical, basic science, and epidemiological aspects 
of the relationship between salt and hypertension; 
review population studies on hypertension control; and 
discuss behavioral approaches to hypertension treat- 
ment. 



U.S. -U.S.S.R. Cooperation on Artificial Heart 
Research and Development 

Scientists in both the U.S.A. and U.S.S.R. recognize 
that present and foreseeable techniques of surgical and 
pharmacological management of acute chronic heart 
failure and shock still leave a substantial fraction of 
patients with compromised or fatally impaired heart 
function. Supportive mechanical devices can assume 
some of the pumping function of the heart and relieve 
its workload. Mutual interest in the development of 
better technology for mechanically assisted circulation 
resulted in 1974 in the Joint Agreement between the 
Government of the U.S.A. and the Government of the 
U.S.S.R. on Cooperation in Artificial Heart Research 
and Development. The Agreement was renewed in 
1977 for 5 years. Since 1974, 58 specialists have been 
exchanged in this area for a total of 31 person-months. 
Two joint symposia have been held. The proceedings of 
the First Joint Symposium on Mechanically Assisted 
Circulation and the Artificial Heart have been published 
in English by the U.S. side, and in Russian by the 
U.S.S.R. side. 

During the past year, joint activities in the area 
focused on the Second Joint U.S. -U.S.S.R. Symposium 
on Mechanically Assisted Circulation and the Artificial 
Heart held in Houston, Texas, September 22-29, 1981. 
Soviet research papers discussed the prospective use of 
implanted circulatory assist systems and artificial hearts 
with a radioisotopic power source; the development of 
methods of circulatory assistance and artificial heart 



50 



ventricles; and numerical modeling of the blood flow in 
the ventricular cavity of the artificial heart. U.S. 
presentations reviewed the status of implantable ener- 
gy systems to actuate and control ventricular assist 
devices; new mechanical techniques of circulatory 
support; and electrical energy converters for practical 
human total artificial hearts. One paper outlined the 
major components of an implantable ventricular assist 
device including 1) energy source, 2) energy transmis- 
sion, 3) energy storage, 4) energy converter, 5) blood 
pump actuator/controller, and 6) blood pump. The 
challenge of an integrated left ventricular assist system 
(LVAS) is a design that is capable of supporting the full 
cardiac output required for the patient. Developing an 
energy system to actuate a permanent implantable left 
heart assist or total heart replacement device must take 
into account the following factors: selection of a source 
of energy to provide mobility; selection of the appropri- 
ate energy conversion technique to translate the energy 
from the source to that form required to actuate the 
blood pump; and definition of methods to control the 
blood pump to meet variable physiological needs. 
Through joint collaboration, U.S. and Soviet scientists 
are sharing their knowledge and laboratory experience 
to advance progress in meeting these challenges. 

Discussion for further joint activities reviewed the 
accomplishments of a three-member delegation visiting 
the U.S.A. in August 1981 for joint in vitro and in vivo 
testing of a Soviet control system received in the U.S.A. 
in July. In conjunction with this visit, U.S. and Soviet 
scientists also developed a potential joint collaborative 
project on biomaterials. The joint project relates to the 
U.S.S.R. symposium presentation "A system of tests 
for assessing hemocompatible properties of polymer 
materials," and involves characterization of the absorp- 
tion of human albumin to three or four well- 
characterized materials. The primary goals are to 
understand better the basic mechanisms of blood- 
material interactions and to assess the comparability 
among laboratories of experimental results. Followup 
arrangements for exchanges of materials and ex- 
perimental results are in progress. 

Plans for further joint activities include the de- 
velopment of joint publications, exchanges of various 
device components by the two sides, and continued 
exchanges of scientists in the following areas: intra- 
aortic balloons, left ventricular assist devices, artificial 
hearts, biomaterials, and in vitro evaluation. 



Venezuela 

A joint U.S. -Venezuela Agreement for Scientific and 
Technological Cooperation in Health was signed in 
August 1980, and discussions are under way to 
implement cooperative efforts under this agreement. 
Venezuelan scientists have a strong interest in coopera- 
tion in the cardiovascular area, focusing on clinical 
research. Possible collaborative efforts in the area of 
Chagas' disease are being investigated. Venezuelan 
and NHLBI investigators are developing a protocol 
which could provide a human model of cardiopathy, to 
prospectively study this disease. 



Yugoslavia 

An agreement between the United States and Yugosla- 
via was signed in May 1973 to encourage research 
projects of mutual interest, utilizing P.L. 480 funds. The 
NHLBI and Yugoslav investigators from the Institute of 
Chronic Diseases and Gerontology are continuing the 
long-term prospective study of the epidemiology of 
cardiovascular disease in a large population of Yugoslav 
men. From its inception in Bosnia in 1962, personnel 
from the Framingham Massachusetts study were 
involved, so that data from this study are statistically 
comparable with the Framingham data. The Yugoslav 
study examined 11,121 men aged 36 to 62 years over a 
period of 7 years and is attempting to relate changes in 
trends of coronary heart disease (CHD) risk factors and 
the prevalence of CHD death to changes in the 
sociocultural environment. Both the urban and rural 
cohorts examined had serum cholesterol levels well 
below the typical U.S. population of Framingham, and 
the Yugoslav incidence of CHD appears to be one- 
fourth that in the U.S.A. Repeat measurements taken 7 
years later showed increases in the average diastolic 
and systolic pressures and increases in the prevalence 
of high blood pressure. Increases were greater in the 
rural than in the urban settings. The Yugoslav popula- 
tion also showed a significant weight increase during 
the 7-year period. Correlation of deaths from CHD and 
serum cholesterol levels were positive. However, 
mortality from all causes increased at the lower serum 
cholesterol levels. The increased deaths in people with 
very low serum cholesterol levels were the result of 
increased respiratory disease deaths, and to lesser 
extent, an increase in the cancer death rate. This study is 
now completed, but combined data analysis continues. 
Six joint publications have resulted to date, and study 
data were presented at the 1980 meeting of the 
American Heart Association Council on Epidemiology, 
the NHLBI Workshop on Cholesterol, and the Euro- 
pean College of Cardiology in Paris. 

The same group of investigators is now beginning a 
new joint project-An Epidemiological Study of Secular 
Trends in CHD Risk Factors in Yugoslavia-which is a 
logical continuation of the previous study. It will 
attempt to answer specific questions that arose during 
the data analysis phase of the earlier study. New 
cohorts of Yugoslavs aged 35 to 64 years will be followed 
to evaluate changes that have occurred in the next 
generation. Cohorts from both the industrial areas and 
the rural areas of Belgrade and from Tuzla, a recently 
industrialized city, are being examined. In April 1981, a 
U.S. epidemiologist helped develop the survey ques- 
tionnaire, and during September 1981, two U.S. 
scientists visited the study sites to finalize pilot study 
plans. Parameters to be measured include total 
cholesterol, high-density cholesterol, triglycerides, and 
serum glucose. Standardization of the biochemical 
parameters will be carried out and monitored with the 
help of the Center for Disease Control (CDC), Atlanta. 
As a result, valid data comparisons from this study with 
U.S. -and WHO-sponsored epidemiological studies will 
be possible. 



51 



Activities with International 
Organizations 

World Health Organization 

In FY 1980, the Institute was designated by the World 
Health Organization (WHO) as its Regional Collabora- 
tive Center for Research and Training in Cardiovascular 
Diseases for the Americas. In this capacity, it provides 
advisory services for WHO and collects and exchanges 
information on cardiovascular diseases. Data pertain- 
ing to all facets of disease control, from basic research 
results to epidemiological studies, and data from 
prevention and control activities form part of this 
exchange. The Director, NHLBI, served as an advisor to 
WHO in the area of long-range planning in cardiovascu- 
lar disease. 

Data from the ongoing U.S. Coronary Artery 
Surgery Study (CASS) continued to be exchanged with 
the participants of the European Coronary Artery Study 
coordinated by WHO. Collaboration among CASS, the 
Veterans Administration Coronary Artery Surgery 
Study, and the European Study continued as planned. 
An expert consultant identified by the NHLBI assisted 
Thailand in its WHO-sponsored national planning 
effort in the cardiovascular area. The recommendations 
of this senior U.S. scientist were approved by the 
National Committee on Prevention and Control of 
Cardiovascular Disease in Thailand for implementation 
within that country's national program. A cardiovascu- 
lar epidemiologist was identified to assist India in a 
WHO-sponsored national planning effort for future 
programs in the cardiovascular area. Similarly, the 
NHLBI identified an expert to aid Bangladesh in its 
development of a cardiovascular disease control pro- 
gram. Using its extensive knowledge of risk factors for 
cardiovascular disease, the NHLBI continues to be 
involved in establishing comprehensive WHO pro- 
grams for the nonpharmacological prevention and 
control of chronic noncommunicable diseases. Pilot 
studies in selected communities are now under way in 
the WHO-sponsored program, Multinational Monitoring 
of Trends and Determinants in Cardiovascular Disease. Data 
from this state-of-the-art study will provide a more 
accurate assessment of trends in heart disease morbid- 
ity and mortality within and between countries. 

Commission of European Communities 

The NHLBI is cooperating with the Commission of 
European Communities (CEC) in the area of extracor- 
poreal oxygenation. Institute staff are working with the 
European Concerted Action on Extracorporeal Ox- 
ygenation (ECAEO) to exchange information about 
ongoing research on how to "transplant" the most 
up-to-date developments in engineering design, 
coagulation problems, and control systems as they 
relate to long-term respiratory support therapy. The 



Director, Division of Blood Diseases and Blood Re- 
sources, met with the Coordinator for the CEC's 
"Concerted Action on Detection of the Tendency to 
Thrombosis" to exchange information. The European 
countries participating in this project are Denmark, 
France, The Netherlands, the United Kingdom, and the 
Federal Republic of Germany. Information has been 
exchanged regarding the CEC Concerted Action on 
Common Standards for Quantitative Electrocardiogra- 
phy. Researchers from the U.S.A., Canada, and Japan, 
as well as researchers from CEC countries, have 
collaborated to develop the protocol for this study. 
Members of the working group for this project con- 
sulted with NHLBI staff. The Institute also provided 
input to the International Bone Marrow Transplant 
Registry organized by the CEC. 



International Visitors and Meetings 

Joint research was carried out in laboratories of the 
Division of Intramural Research by 75 international 
investigators. They came from Argentina, Canada, the 
Federal Republic of Germany, France, Italy, Japan, The 
Netherlands, Poland, Sweden, Turkey, and the United 
Kingdom. Many foreign scientists participated in the 
Seventh U.S. National Conference on High Blood 
Pressure Control as well as several state-of-the-art 
workshops and consensus-development symposia 
organized by NHLBI during FY 1981 . 

Extramural Programs 

During FY 1981, the NHLBI awarded 17 contracts and 
eight grants to the following foreign countries: Argenti- 
na, Australia, Canada, Denmark, Israel, Italy, Roman- 
ia, and Sweden. They supported mainly cooperative 
epidemiological studies or foreign components of 
national clinical trials. Seven fellowships were awarded 
U.S. to scientists for training in the following countries: 
Belgium, Canada, Denmark, the Federal Republic of 
Germany, Israel, and the United Kingdom. 

In one study, the effect of migration on the familial 
aggregation of blood pressure on Tokelau Islanders 
who migrated from an atoll in the South Pacific to New 
Zealand was investigated. This collaborative multidisci- 
plinary study is focusing on the changes in blood 
pressure and other variables important in cardiovascu- 
lar disease. The study is unique in that the population 
was surveyed before migration was completed and that 
both the nonmigrant population (in Tokelau) and the 
migrant population (in New Zealand) are subject to 
longitudinal followup. Migrants showed a considerable 
increase in the prevalence of hypertension and a less 
marked increase in mean blood pressure. Obesity, 
which is increased in the migrants, is clearly a factor in 
their elevated blood pressure. 



52 



7 



NATIONAL INSTITUTE 
ON AGING 



Introduction 

Between now and the year 2000, the segment of the 
population that is 60 years old or older will grow faster 
than any other age group in both the developed and 
developing world. Considerations surrounding this 
demographic development have prompted the com- 
munity of nations to convene the United Nations World 
Assembly on Aging (UNWAA) to be held at the 
Hofburg Palace in Vienna from July 25 to August 6, 
1982. The agenda for the conference includes health as a 
primary humanitarian issue for consideration. Col- 
laborative efforts are under way to extend the mandate 
of the National Institute of Aging (NIA) beyond the 
borders of the United States in drafting, with the World 
Health Organization, a program of action for the 
UNWAA. The goals of the program would include a 
coordinated research and development program to 
increase the independence of older people and their 
contribution to society and to promote health mainte- 
nance and well-being of the elderly. 

Planning and priority-setting in developing a 
global program must depend upon evolution in specific 
areas, including health costs, epidemiology, the burden 
of illness, the avoidance of trivial or duplicative 
research, the state of the art, and the availability of 
resources. 

Summary of Bid International 
Programs and Activities 

Cooperation with International Agencies - World 
Health Organization 

The Institute's association with the World Health 
Organization (WHO) was formalized in the May 1981 
designation as the first WHO Collaborating Center for 
Joint Cooperation on Research on the Care of the Aged. 
Under the terms of the agreement, both WHO and NIA 
would be involved in the followup of the December 
1980 WHO Preparatory Conference for the World 
Assembly on Aging in Mexico City, for which the 
Institute provided financial and planning support. 

The major themes of the Conference were based on 
the WHO strategies of Health for All by the Year 2000, 
Services and Technology, Intersectoral Cooperation, 
and Program of Future Action. Recommendations for 
the WHO Global Programme for Care of the Aged were 
offered. Research on the problems of the aging, and 



particularly health services research, were considered 
of the highest priority. 

In July 1981, the NIA Associate Director for 
Epidemiology, Demography, and Biometry chaired the 
WHO Workshop on Policy Oriented Research on 
Health Care of the Elderly. This workshop dealt 
primarily with population-based health and social 
research. The recommendations will be used in the 
preparation of documents for the 1982 United Nations 
World Assembly on Aging. 

The fifth WHO-sponsored meeting of directors of 
national institutes of gerontology hosted by the NIA is 
planned for The White House Conference on Aging in 
November/December 1981. Representatives from the 
following member nations will be invited: Senegal, 
Brazil, Costa Rica, Venezuela, India, Israel, France, 
German Democratic Republic, Hungary, The Nether- 
lands, Norway, Romania, Sweden, United Kingdom, 
Union of Soviet Socialist Republics, Australia, Japan, 
and the People's Republic of China. 

Extramural Program 

Eight grants to foreign investigators, or involving 
studies of societies, cultures, or groups in other regions 
of the world, were funded by the Institute during FY 
1981 . Support for these multiyear awards totalled about 
$632,869, and represented slightly over 1 percent of the 
total FY 1981 NIA extramural support program, as 
opposed to less than 1 percent in preceding years. 

The versatility of the areas being supported is in 
keeping with the multidisciplinary nature of the 
Institute's biomedical and behavioral sciences pro- 
grams. Some projects are: basic studies on defective 
enzymes in aged animals by an investigator at the Israel 
Institute of Technology; testing in Belgium of a genetic 
developmental theory of aging at the level of the 
species, using Drosophila melanogaster; retirement 
and aging in cross-cultural perspective involving situa- 
tions of older people in China, Russia, and several 
Eastern European countries; and studies of adult twins 
reared apart in Sweden and Finland to learn about aging 
changes in cognitive and noncognitive domains. 

Conferences, Seminars, and Meetings 

In May 1981, the Institute, in cooperation with its 
National Advisory Council on Aging, held a Seminar on 
International Developments in Aging to inform the 
Council members, staff, and guests of the global 



53 



concerns and activities that bear upon the "greying of 
nations," to facilitate exchanges among the key orga- 
nizations, and to consider health-related research as a 
vital part of the 1982 United Nations World Assembly 
on Aging. Guest speakers included the Chairman of the 
WHO Global Advisory Committee on Medical Re- 
search; the Chairman of the Subcommittee of Health 
and Behavior of the Global Committee; Director, 
Programme Management, WHO Regional Office, 
Europe; Deputy Director, WHO Office of the Americas 
(PAHO); and the U.S. State Department Coordinator 
for the 1982 U.N. World Assembly on Aging. 

The following seminars were conducted during the 
last year: 

•High Altitude Research, Cayetano Heredia Universi- 
ty, Lima, Peru 

•Intracranial Self Stimulation of an Anti-Stress Factor, 
Anochin Research Institute and First Moscow Medical 
School, U.S.S.R. 

•Models of Cardiac Hypertrophy, Universitat Tubigen, 
Germany 

•Mechanism of Action of Glucagon in Liver Mitochon- 
dria, Nenchi Institute of Experimental Biology, War- 
saw, Poland 

•Photocoustic Spectroscopy, Hyderabad, India 
•Cardiovascular and Behavioral Interactions, Koln 
University, Germany 



Intramural Programs and Activities Including NIH 
Visiting Program 

The Intramural Research Program of the National 
Institute on Aging is conducted at the Gerontology 
Research Center located in Baltimore, Maryland. Dur- 
ing fiscal year 1981, the Center's international activities 
involved research training for 33 Visiting Scientists, 
Fellows, and Associates from 15 countries: Australia, 
Canada, Chile, Egypt, Finland, Greece, Hungary, 
India, Israel, Italy, Japan, Poland, Sweden, Taiwan, 
and Turkey. The foreign nationals worked in the NIA 
laboratories, where investigators conduct quantitative 
and qualitative research into many of the biological, 
physiological, medical, and behavioral factors associ- 
ated with animals, including humans. 

In addition to the geriatric research training 
opportunities afforded within the NIA intramural 
program, the GRC hosted visits by international 
delegations such as members of the Georgian Academy 
of Sciences, U.S.S.R., who conferred with GRC staff on 
human aging studies conducted in this country and 
exchanged ideas about such studies in their respective 
countries. This Soviet visit was sponsored by the 
U.S. -based Institute for the Study of Man. 



54 



8 



NATIONAL INSTITUTE 

OF ALLERGY 

AND INFECTIOUS DISEASES 



Introduction 

The National Institute of Allergy and Infectious Dis- 
eases was formally established by law in 1948 as the 
National Microbiological Institute. Its change of name 
in 1955 reflected the increased emphasis on basic 
research in communicable diseases and immunological 
disorders. Following the dissolution of the NIH Office 
of International Research in 1968, NIAID assumed the 
major responsibility for tropical medicine activities. 
Intramural research is carried out by approximately 600 
staff members in Bethesda, Maryland, and the Rocky 
Mountain facilities in Hamilton, Montana. The NIAID 
extramural research program, however, constituted 
more than 80 percent of the total budget in FY 1981. 
Academic and research institutions carry out these 
extramural activities through research and training 
grants and contracts. 

Infectious diseases continue to be the most fre- 
quent reason for patients to seek medical attention in 
industrialized societies, and they are still the leading 
cause of reported morbidity and mortality in develop- 
ing countries. The results of the domestic NIAID 
program, therefore, have inherent and far-reaching 
relevance for national health authorities outside the 
United States and for agencies that cooperate with them 
in applying this new knowledge and technology to 
disease prevention and control. 

During FY 1981, NIAID continued to assign special 
priority in its Tropical Medicine Program to filariasis, 
leishmaniasis, leprosy, malaria, schistosomiasis, and 
trypanosomiasis. These are the six diseases targeted for 
intensive research by the WHO/UNDP/World Bank 
Special Program on Tropical Disease Research (TDR). 
Reporting these tropical diseases separately facilitates 
communication and coordination with WHO and other 
international agencies. The NIAID Tropical Medicine 
Program also includes other infectious diseases in 
which international collaboration is essential to comple- 
ment the domestic research effort. These activities are 
discussed in this report under general parasitology; 
tropical bacteriology, mycology, and virology; rickett- 
sioses and vector pathogens. Additional conditions that 
constitute more serious public health problems in 
developing countries than in the United States are the 
subject of international collaboration but are not 
included in the budgetary figures for the Tropical 
Medicine Program. Examples include: gastroenteritis 



other than cholera, hepatitis, acute respiratory illness, 
and sexually transmitted diseases. 

General parasitology consists of research on the 
remaining parasites of importance to human health and 
basic research projects, parasitology research training, 
and career development awards which could not be 
assigned to any one of the six targeted diseases. Basic 
research in parasitology is a prerequisite to further 
understanding and advances in the prevention or 
control of the five parasitic diseases of TDR. Indeed, the 
disease-oriented initiatives of the Public Health Service 
(PHS), Army, Navy, USAID, and WHO have evolved 
from and will continue to rely on basic research 
breakthroughs to achieve their goals of vaccine and 
drug development or vector control. 

During FY 1981, tropical bacteriology awards (7 
percent) were heavily concentrated in research on 
cholera and related organisms (12), tuberculosis and 
mycobacteria other than leprosy (4), leptospirosis (1), 
nonvenereal treponematoses (1) and yersinia (1). 
Although WHO has recently established a Global 
Diarrheal Disease Control Program (DDC) with a major 
research component in epidemiology, improved drugs, 
and vaccine development, NIAID activities in viral and 
bacterial diarrheas other than cholera are not a formal 
part of the Tropical Medicine Program. 

Histoplasmosis (5) and coccidioidomycosis (2) 
contribute the bulk of the tropical mycology area (2 
percent). The rickettsiae program (3.7 percent) is 
directed primarily toward Rocky Mountain Spotted 
Fever. Tropical virology (8.4 percent) includes 21 
research projects in arboviruses (12), rabies, and other 
viral agents of public health importance (e.g., Lassa 
fever) which are not endemic to the U.S.A. Vector 
pathogen activities (7.4 percent), by contrast, consisted 
of 26 projects to study the mosquito (14), fly (2), tick (2), 
mite (1), and snail (4) vectors of human viral, rickettsial, 
and trematode diseases. 

Foreign investigators are eligible to compete with 
U.S. investigators for NIAID grants and, under special 
conditions, for "sole resource" contract funds. The bulk 
of NIAID-sponsored international research, however, 
is generated through NIH awards to U.S. -based 
scientists and institutions. NIAID grants for Interna- 
tional Collaboration in Infectious Diseases Research 
(ICIDR) are intended to provide such a linkage for 
research to be done outside the country. The ICIDR 
program, as well as the NIAID-supported Tropical 



55 



Disease Research Units (TDU) within the United States, 
will be discussed later in more detail. Additional 
mechanisms include bilateral medical research prog- 
rams and the Special Foreign Currency (P.L. 480) 
Program (Coordinated for NIH by the Fogarty Interna- 
tional Center) in six countries. MAID was most actively 
involved in FY 1981 with Argentina, Australia, Brazil, 
Colombia, the Dominican Republic, Egypt, France, 
India, Israel, Japan, Kuwait, Mexico, The Netherlands, 
Nigeria, Pakistan, Panama, the People's Republic of 
China, Poland, Sierra Leone, Sudan, Sweden, Switzer- 
land, Thailand, the United Kingdom, and Venezuela. 
On September 24, 1981, MAID signed a Participat- 
ing Agency Service Agreement (PASA) with the U.S. 
Agency for International Development (USAID) to 
administer a multiple-year project entitled "The 
Epidemiology and Control of Arthropod-Borne Dis- 
eases in Egypt and Israel/The first-year funding at $1.5 
million will provide for research contracts with the 
Hebrew University (Jerusalem) and Ain Shams Uni- 
versity (Cairo), as well as for the participation of U.S. 
scientists from other Federal agencies and universities. 
The initial emphasis will be on the epidemiology and 
epizoology of three diseases: Rift Valley Fever, malaria, 
and leishmaniasis. 

Bilateral Agreements and Other 
Country-to-Country Activities 

MAID conducts scientific exchange and collaborative 
research through a variety of mechanisms which extend 
from informal direct contact between investigators to 
formal agreements for cooperation between the Gov- 
ernments of the U.S.A. and other countries. Because of 
the MAID research responsibilities in tropical diseases, 
microbiology, and vaccine development, the Institute 
has a unique need to foster cooperation with scientists 
and institutions in developing countries. In recent 
years, there has been a proliferation of formal bilateral 
science and technology agreements with developing 
countries. In addition, there has been a trend for 
existing and new bilateral programs to move into 
additional areas such as immunology and genetic 
engineering. 

Argentina 

In February 1981, the Minister of Health of Argentina 
visited MAID to discuss the prospects for expanded 
collaboration in Chagas' disease (American trypanoso- 
miasis) and Argentina hemorrhagic fever under the 
terms of the U.S. -Argentina Science and Technology 
Agreement. A scientist in the Laboratory of Parasitic 
Disease presently collaborates with the Instituto "Fatala 
Chaben" (Buenos Aires) on the cell biology of Trypano- 
soma cruzi strains and single-cell isolate clones. 

Australia 

During FY 1981, there was an exchange of information 
between the Governments of Australia and the U.S.A. 
on recombinant DNA guidelines and policies. MAID 
continued its productive extramural collaboration in 
immunology with scientists at the Walter and Eliza Hall 



Institute of Medical Research. Three active grants there 
supported research on the development of model 
parasite vaccines, mechanisms of lymphocyte-antigen 
interactions, and T cell development in the thymus. 

Bangladesh 

MAID collaborative research with the International 
Center for Diarrheal Disease Research/Bangladesh is 
with the Laboratory of Infectious Diseases in the 
epidemiology of rotavirus infection. 

Brazil 

During FY 1981, four of the 10 active ICIDR awards 
totalling $1,128,808 went to the U.S. investigators for 
collaborative studies in Brazil. Cornell University 
Medical College collaborates with the University of 
Bahia on Chagas' disease and the endemic forms of 
cutaneous, mucocutaneous, and visceral leishmaniasis. 
The Harvard School of Public Health is involved in 
collaboration with the University of Bahia and the 
Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, 
on Chagas' disease and schistosomiasis. The presence 
of three full-time U.S. scientists has led to the 
establishment of a multidisciplinary Brazilian-U.S. 
team with competence in the fields of epidemiology, 
clinical medicine, immunology, and entomology. In 
February 1981, the University of Bahia hosted a 1-day 
symposium to review the research activities of Brazilian 
and U.S. scientists associated with the projects. 

The University of South Florida is the recipient of 
an ICIDR exploratory grant to collaborate with scientists 
at FIOCRUZ on studies of the spread of schistosomiasis 
in newly developed agricultural colonies in Northeast 
Brazil (Piaui). A Columbia University investigator is 
involved in a collaborative study with the Federal 
University of Rio de Janeiro to use lectins to study the 
cell surface carbohydrates of virulent and avirulent 
forms of Leishmania. 

Intramurally, collaboration continues with the 
University of Goias (Goiana) on the HLA tissue-typing 
of patients with Chagas' disease. More detailed studies 
of the immune response of selected patients is being 
planned. FIOCRUZ and Conselho Nacional de Pes- 
quisa (CNPq) scientists are exploring with MAID 
collaboration in tropical medicine. 

Canada 

MAID supports an investigator-initiated grant award at 
the University of Manitoba on the suppression of the 
IgE response. 

Colombia 

Tulane University's collaborative research with COL- 
CIENCIAS (Colombian Fund for Research) will con- 
tinue under the ICIDR mechanism with emphasis 
directed toward both epidemiological and basic biologi- 
cal investigations of selected vector-borne diseases, 
especially filariasis and trypanosomiasis. As examples 
of the range of the ICIDR activities, Dipelatonema 
perstans microfilaremia has been documented in 31 
percent of the population of the Amazon Basin (Guainia 
Territory). In the laboratory, an enzyme-linked, im- 
munosorbent (ELISA) test is being used to study levels 



56 



of humoral immunity in the serum of patients with 
filariasis. The Cali Center has also succeeded in 
attracting complementary grant support from WHO 
and the Canadian International Development Research 
Center. 

Congo/Brazzaville 

At the request of the U.S. Ambassador, MAID scientist 
administrators visited Brazzaville in November 1981 to 
explore possible linkages in tropical medicine between 
MAID and the People's Republic of the Congo. 

Czechoslovakia 

The Laboratory of Immunology collaborates with the 
University of Prague on immunoglobulin genetics, 
including the regulation of gene expression and 
lymphoid differentiation. 

Dominican Republic 

The Laboratory of Parasitic Diseases continues its 
collaborative studies of leishmaniasis with the Instituto 
Dermatologico (Santo Domingo). The Dominican Re- 
public has a uniquely high incidence of diffuse 
cutaneous leishmaniasis, a rare manifestation previous- 
ly reported in Ethiopia and Venezuela. It appears that 
the Dominican leishmanial strain is different from the L. 
mexicana and L. brasiliensis prevalent elsewhere in Latin 
America. Studies on four Dominican patients at the 
Clinical Center, however, indicate that the major 
determinant may be an HLA-linked primary macro- 
phage-antigen-handling defect. These patients did not 
respond to Pentostam but had a good initial response to 
Amphotericin B. Of interest is that one patient with 
bilaterally symmetrical lesions responded to local 
hyperthermia. 

Egypt 

MAID has also been involved in collaborative research 
with Egyptian investigators for more than a decade, 
most recently under the terms of the U.S. -Egypt 
Agreement for Collaboration in the Areas of Science 
and Technology. During FY 1981, MAID collaboration 
was primarily through P.L.-480 projects. Because new 
P.L.-480 awards stopped in FY 1981, MAID will phase 
out some of these projects. In other instances, MAID 
staff will work with U.S. and Egyptian scientists to 
obtain alternate sources of funding. 

In addition to direct involvement, MAID is 
involved in collaborative efforts with CDC- 
administered P.L.-480 projects. The Laboratory of 
Infectious Diseases and the NIAID-funded Infectious 
Enteric Diseases Study Center at the University of Texas 
(Houston) provide virologic and bacterial support, 
respectively, to the Diarrheal Diseases Project at the 
Epidemiology Study Center in Bilbais. 

Federal Republic of Germany 

The exchange of guidelines and technical information 
continues with the Federal Ministry for Research and 
Technology (BMFT). MAID also provides grant sup- 
port to the Max Planck Institute for Biology on the 
polymorphism of the major histocompatibility com- 
plex. 



Finland 

In FY 1981, MAID extended its contract with the 
Central Public Health Laboratory to provide followup 
studies of children immunized with meningococcal 
type A vaccine from 1974 to 1978. The original contract 
resulted from a 1973 request from the Finnish National 
Board of Health for assistance in dealing with an 
epidemic of that disease. The new contract includes 
evaluation of the response to Hemophilus influenza, type 
B vaccine administered as a control in the 1974 efficacy 
trials. MAID also supports one grant to the University 
of Helsinki to study the regulation of immune response 
by specific factors. 

France 

During FY 1981, MAID continued the support it has 
provided for 20 years to 1980 Nobel Laureate Dr. Jean 
Dausset on skin grafts and surface leukocyte antigens. 
Intramural scientists collaborate with the Institut Pas- 
teur on genetic studies of immunoglobulins and other 
serum proteins; with the CNRS on the structure and 
activity of immunologically important cells and pro- 
teins; and with the Faculty of Medicine/Brest on 
tick-borne disease agents. An INSERM scientist was 
hosted for 4 months to study the generation of 
suppressor and cytotoxic t cells directed to paternal 
antigens in postpartum mice. 

Ghana 

The Laboratory of Parasitic Diseases increased its 
scientific exchange and developed plans for a collabora- 
tive project on the chemotherapy and immunology of 
filariasis with investigators at the Tamale Hospital. 

Haiti 

The Tulane ICIDR Program has developed a collabora- 
tive project in Haiti on the epidemiology of filarial 
infection at the Institut Frangais d'Haiti. 

Hong Kong 

An MAID science administrator visited the Chinese 
University of Hong Kong in December 1980 to review 
the antiviral research project there which screens 
Chinese traditional herbs. As a result, two MAID 
contract recipients evaluated "guan-zhong," which had 
shown anti-influenza activity in vitro in animal models. 
While both investigators documented modest effects of 
a partly purified herbal extract, they also demonstrated 
in vitro and in vivo toxicity. As the toxic and active agents 
may be different, MAID has recommended that further 
characterization be carried out. 



India 

MAID has participated over the years in collaborative 
research with Indian investigators, funded largely 
through the P.L.-480 program. In February 1980, the 
Indian-U.S. Working Group on Health of the Joint 
Science and Technology Committee met in New Delhi 
to review and redefine priority diseases for collabora- 
tive research. The mutually agreed upon areas for 
emphasis were: diarrheal diseases; filariasis; hepatitis; 
leprosy; malaria; recombinant DNA technology; 



57 



rheumatic fever and sequelae; and tuberculosis. NIAID 
reviewed the status of these activities with the Senior 
Deputy Director, Indian Council for Medical Research 
(ICMR), during a visit to NIH in June 1981. 

In February 1980, the Joint Working Group on 
Health endorsed the concept of an Indo-U.S. Workshop 
on Diarrheal Diseases. The Workshop is now scheduled 
to be held at the ICMR Headquarters in New Delhi from 
February 17 to 20, 1982. Approximately 10 U.S. and 30 
Indian scientists will participate in sessions devoted to 
promoting scientific exchange and collaboration in 
epidemiology; ecology; bacterial, viral, and parasitic 
agents; clinical management; infection-nutrition in- 
teraction; immune mechanisms; and the application of 
recombinant DNA technology to diarrheal disease 
research. 

During FY 1981, collaboration was begun with the 
Kothari Centre for Gastroenterology (Calcutta) on the 
axenic culture of Entameba histolytica and the nutritional 
iron status of patients with amebiasis. 

An NIAID scientist visited the Tuberculosis Re- 
search Center (Madras) for 3 weeks in September 1981, 
in a continuation of a collaborative effort which began in 
1975 on the immunology of filarial infections and the 
pathogenesis of tropical eosinophilia and lymphan- 
giitis. This "no-cost" proposal is now moving into two 
new clinical areas: the long-term effect of diethylcarba- 
mazine (DEC), mebendazole, and DEC-mebendazole 
on lymphatic pathology and the development of 
elephantiasis; and the natural history of asymptomatic 
microfilaremia with and without chemotherapy. 

Another NIAID scientist continues his collabora- 
tive studies at the National Institute of Virology (Poona) 
on the epidemiology of hepatitis in India. With the 
application of recently developed laboratory tests, it is 
now apparent that the massive water-associated out- 
break of hepatitis in Delhi in 1955-56 was neither 
hepatitis A nor B. Ongoing studies indicate that non-A, 
non-B hepatitis is a common source of epidemic and 
sporadic hepatitis in India. NIAID has been able to 
produce hepatitis in chimpanzees following the ino- 
culation of infectious Indian material, but has not yet 
recovered an etiologic agent. Efforts are now under way 
to develop a study with the National Institute of 
Virology on the epidemiology of hepatitis of pregnancy 
and childhood cirrhosis. 

During FY 1981, the Government of India made a 
policy commitment to eliminate leprosy as a public 
health problem by the end of the century. Indo-U.S. 
collaboration in leprosy has been shared within the PHS 
among the National Center for Hansen's Disease in 
Carville, Louisiana, NIAID, and CDC. 

An ICIDR exploratory grant has been awarded to 
the University of Hawaii to collaborate with the Aligarh 
Muslim University on the in vitro cultivation of human 
malarial parasites isolated in India, the drug susceptibil- 
ity of Plasmodium falciparum, and the culture of Indian P. 
vivax strains in vitro. An NIAID scientist visited the 
Central Drug Research Institute (Lucknow) in Septem- 
ber 1981 to complete the preparation of two collabora- 
tive protocols, entitled: "The identification of im- 
munogens and immunosuppressive molecules in pri- 



mate malarias" and "Studies on immunity to the sexual 
stages of the malarial parasite." 

During FY 1981, plans for a fixed-site Indo-U.S. 
Workshop on Recombinant DNA were modified in 
favor of the visit of a team of four U.S. scientists led by 
the current Deputy Director of NIAID in March 1982. 
The team will become familiar with the leading Indian 
scientists and institutions active in this area and 
develop recommendations for immediate scientific 
exchange and opportunities for longer-term NIAID-, 
NHLBI-, and FIC-cosponsored and -provided funds for 
a Conference-Workshop on Rheumatic Fever in the 
1980's (New Delhi: March 2-5, 1981). Although de- 
veloped within the Indo-U.S. joint Health Program, 
scientists from Asia, the Western Pacific, the Near East, 
Europe, and Latin America participated. The American 
Heart Association coordinated the U.S. effort. Publica- 
tion of the proceedings is expected in FY 1982. While it is 
too early to evaluate the extent to which the Conference 
served as a catalyst for collaborative research, efforts are 
under way between the University of Tennessee and 
the ICMR Streptococcal Typing Center (New Delhi) to 
study the epidemiology of group M streptococcal 
protein in India. 

Israel 

Two intramural laboratories collaborate with the 
Hadassah Medical Center (Jerusalem). The Laboratory 
of Streptococcal Disease is involved in studies which 
relate the electron microscopic appearance of bacteria to 
their structure and function. The Laboratory of Micro- 
bial Immunology is active in the characterization of 
surface IgG in the clones of a murine B cell lymphoma. 
The three NIAID extramural grants to Israeli investiga- 
tors are concerned with: the bioenergetics and control of 
bacterial behavior; the exploration of new approaches to 
marrow and organ transplantation; and the differentia- 
tion and activity of mast cells in culture. 

Italy 

During FY 1981, NIAID supported three extramural 
projects within the Italy-U.S. bilateral Understanding 
on Cooperation in the Field of Health and Medicine. 
These awards to U.S. scientists at Roswell Park 
Memorial Institute, Temple University, and Rockefeller 
University are in the areas of biosynthesis of bacterial 
cell walls and membranes, immunological studies with 
cultured human lymphocytes, and studies of myeloma 
protein and antibodies. 

Japan 

NIAID is currently involved in two Japan-United States 
initiatives. The first is the U.S. -Japan Cooperative 
Medical Science Program (JCMSP), initiated in January 
1965. Under the terms of this agreement, both countries 
have undertaken joint cooperative biomedical research 
in diseases of particular importance in Asia. Under 
Public Law 86-610 (the International Health Research 
Act of 1960), the State Department coordinates foreign 
relations and policy while DHHS is responsible for the 
scientific elements of the program. NIAID has been the 
lead Institute within NIH and DHHS since 1968. 



58 



Although the JCMSP operates as a bilateral program, 
scientists from other countries and/or international 
agencies often participate. Applications submitted 
within the context of this program by U.S. scientists 
compete for available funds on the basis of scientific 
merit without a special NIAID budget set-aside. 
Japanese scientists, on the other hand, depend upon 
the Program to facilitate their funding proposals. 

At the present, the JCMSP consists of panels on: 
leprosy, tuberculosis, cholera, hepatitis, parasitic dis- 
eases (schistosomiasis and filariasis), viral diseases 
(arboviruses, rabies, rotaviruses), environmental 
mutagenesis and carcinogenesis, and malnutrition. 
These panels meet annually either in the U.S.A. or 
Japan. The Director of NIAID and staff members serve 
as the Secretariat to the U.S. Delegation to the JCMSP 
and to six of the panels. The Third Five-year Report 
(1975-1980) of the JCMSP became available in Septem- 
ber 1980. 

JCMSP Panel Meetings during FY 1981 included 
the following: Hepatitis (Hakone: November 20-21, 
1980); Leprosy (Bethesda: July 13-14, 1981); and Tuber- 
culosis (Bethesda: July 13-15, 1981). The U.S. -Japan 
Immunology Symposium (Tokyo: October 13-15, 1980) 
focused on four areas: the regulation of immune 
response by MHC and idiotype; molecular biology of B 
lymphocyte differentiation; hybridomas and functional 
cell cloning; and differentiation and functions of human 
lymphocyte subsets. 

Following the October 1980 Immunology Sympo- 
sium, the joint committee approved in principle the 
inclusion of immunology within the JCMSP, but 
referred the matter to the Subcommittee on Program 
Review and Planning for further deliberation. In 
February 1981, the subcommittee met in Honolulu and 
recommended that the new area be known as the 
Immunology Board to reflect both its disciplinary, 
rather than disease, orientation and the involvement of 
the Ministry of Education. At its July 16-17, 1981 
meeting in Bethesda, the joint committee explored the 
problem of how to reduce spending, especially travel, 
without sacrificing the mission of the program. The 
joint committee made the policy recommendation that 
unilateral changes were not in order due to the different 
funding mechanisms in the two countries. Mechanisms 
for effecting changes and cost reductions will be 
discussed at the next subcommittee meeting (Honolulu: 
February 11-12, 1982). 

On May 1, 1980, the President of the United States 
and the Prime Minister of Japan signed the Japan-U.S. 
Science and Technology agreement for Non-Energy 
Cooperation, which will be separate from, but coordin- 
ated with, the JCMSP. Within this second bilateral 
program, NIAID has lead responsibility for three 
program areas: immunization (vaccine development), 
recombinant DNA research, and antiviral agents. 

Since then, guidelines for recombinant DNA 
research have been exchanged, and the Japanese 
Coordinator has participated in the meetings of the U.S. 
Recombinant DNA Committee. In November 1980, 
NIAID/NIH hosted an informal group of Japanese 
interferon researchers touring the U.S. The First 



Meeting of the U.S. -Japan Cooperative Program for 
Recombinant DNA Research (Honolulu: February 2-5, 
1981) continued the exchange of scientific information 
on host-vector systems and risk assessment. The 
participants also developed a Memorandum of Under- 
standing, subsequently signed by the U.S. and 
Japanese coordinators, which provided the basis for 
activities in FY 1981-82. 

At the first Meeting of the U.S. -Japan Program for 
Cooperation in Science and Technology (Tokyo: 
September 24-25), both countries agreed to continue to 
develop recombinant DNA research activities within 
the Science and Technology Program. The technical 
aspects of vaccine development and antiviral agents, 
however, will remain with the appropriate JCMSP 
panel. Matters requiring policy review and decisions 
will be referred to the U.S. Chairman of the Science and 
Technology Program. 

Outside the two formal bilateral programs, three 
intramural laboratories have ongoing collaboration 
with Japanese scientists. One is actively involved with 
the University of Tokyo in the fractionation of lymphoid 
cell subsets with lectins that specifically bind to cell 
surface glycan differentiation markers. The Rocky 
Mountain facilities also maintain collaboration with 
scientists at the National Institutes of Health in Tokyo 
on tick-borne disease agents and the characterization of 
human papovaviruses. 

Kuwait 

An NIAID scientist traveled to Kuwait from April 3 to 
10, 1981, as a consultant to the Ministry of Public Health 
in the development of a national allergic disease 
program and the feasibility of an Allergy Research 
Center. 

Mexico 

The University of Washington has an exploratory 
ICIDR award to work with the Institute Nacional 
Politecnico (Mexico City) on the serodiagnosis of 
subclinical leprosy. The Laboratory of Parasitic Diseases 
continues collaborative research with Mexican scien- 
tists and the Center for the Study of Amebiasis (Mexico 
City) which began over 10 years ago. 

Netherlands 

Three intramural laboratories have ongoing collabora- 
tive research activities with counterparts in The Nether- 
lands: the State University of Utrecht is involved in 
studying the specificity of immune responses; The 
Netherlands' Red Cross Book Transfusion Service is 
studying the mechanisms of immune recognition of 
viral antigens; and the Catholic University of The 
Netherlands is studying the taxonomy, ecology, and 
colonization of parasitic arthropods of medical impor- 
tance. Two research contracts with the University of 
Leiden are concerned with the acquisition of homozy- 
gous typing cells and antisera to HLA-A, -B, and -C loci 
and B cells. 

Nigeria 

Ohio State University has an active ICIDR exploratory 



59 



grant with the University of Nsukka to study the 
biological control of mosquitoes which transmit malaria 
by Bacillus thuringiensis. A Nigerian Visiting Fellow is 
carrying out investigations on the binding of red blood 
cells infected with malaria to the endothelium of blood 
vessels. NIAID staff have also participated actively in 
the development of the biomedical research component 
of the U . S . -Nigeria Joint Task Force on Health Coopera- 
tion (Bethesda: February 9-12, 1981). 

Pakistan 

While the University of Maryland International Center 
for Medical Research (ICMR) at the Pakistan Medical 
Research Center (Lahore) terminated in May 1980, 
NIAID continues to support an investigator-initiated 
project on the ecology of mosquitoes in Pakistan and the 
genetic control of Anopheles culicifacies, an important 
vector of malaria in that country. 

Panama 

During FY 1981, NIAID supported the Gorgas Memo- 
rial Laboratory through the Gorgas Memorial Institute 
(Washington, D.C. ) for investigations in Panama on the 
transmission and reservoirs of the St. Louis virus in 
tropical ecosystems. The Gorgas Institute also collabo- 
rates with the NIAID-supported Yale Arbovirus Re- 
search Unit (YARU) on the epidemiology of the yellow 
fever virus. 

People's Republic of China 

The U.S.-PRC Joint Committee on Science and Technol- 
ogy in Medicine and Public Health held its first meeting 
in Beijing in June 1979. At that time, NIAID was 
assigned lead responsibility for immunology, and 
secondary responsibility with the Centers for Disease 
Control (CDC) in parasitology and infectious diseases. 
The parasitic and infectious diseases emphasized in the 
bilateral health protocol are: malaria, schistosomiasis, 
hepatitis, and influenza. NIAID subsequently assumed 
the lead role in recombinant DNA research. 

As a result of the exchange visits of the U.S. and 
Chinese coordinators in FY 1980, the protocol for 
cooperation in immunology was modified for FY 
1981-82 to include the immunology of infectious and 
parasitic diseases; cancer; diseases of the immune 
system, including primary immune deficiency diseases; 
and autoimmunity and allergy and skin and organ 
transplantation. The research approaches will involve 
immunobiology, immunogenetics, molecular im- 
munology, immunopharmacology, and clinical im- 
munology. The Immunology Work Plan provides for 
scientific exchange, research training, working groups, 
and collaborative research in immunogenetics and 
clinical immunology. The U.S.-PRC Joint Committee 
endorsed these modifications at its second meeting 
(Tianjin: November 20-21, 1980). 

During May 1981, NIAID hosted the 3-week visit of 
three Chinese allergists who toured clinical and re- 
search facilities in Washington, Baltimore, New York, 
Boston, and La Jolla. 

NIAID signed an interagency agreement ($37,000 
in FY 1981) with CDC in September 1981, to share costs 
on the collaborative protocol with the Institute of 



Virology (Beijing) and Shanghai First Medical College to 
study the efficacy of the NIH inactivated hepatitis B 
vaccine in the prevention of transmission of infection 
from hepatitis B antigen (HBsAg) carrier mothers. 
Comparison of the antigenicity of the U.S. -produced 
vaccine in Chinese adult volunteers is under way. 
NIAID also sponsored the 3-month visit of the Deputy 
Director of the Department of Hepatitis and Influenza, 
National Serum and Vaccine Institute (Beijing), to 
NIAID and the Bureau of Biologies to become familiar 
with hepatitis vaccine production and quality control 
techniques. 

Poland 

During FY 1981, NIAID involvement in the Polish-U.S. 
Agreement on Cooperation in the Field of Health 
consisted of two P.L.-480 projects with extramural 
scientists on the immunochemistry of Shigella lipopoly- 
saccharides and the role of macrophage surfaces in the 
regulation of immune response. 

Sierra Leone 

NIAID and FIC continued to share the costs of an 
interagency agreement with CDC for studies on 
Mastomys natalensis (a multimammate mouse) and Lassa 
fever in rural Sierra Leone. The project attempts to 
characterize the populations ofM. natalensis; determine 
the relationship of genetic subpopulations of mice to 
transmission of Lassa fever to humans; describe the 
epidemiologic and socioeconomic factors associated 
with transmission in the village and develop techniques 
to prevent rodent-human transmission. 

South Africa 

NIAID currently supports a research contract with the 
State University of New York (Syracuse) which will 
provide for collaboration with the Bureau of Biologies 
(FDA), the South African Institute for Medical Research 
(Johannesburg), and the University of Cape Town to 
test the efficacy of the new Bureau of Biologies' 
meningococcus, type B polysaccharide vaccine in 
infants and young children during the ongoing 
epidemic of that disease in South Africa. Safety and 
efficacy studies had previously been carried out in U.S. 
children at NIAID Vaccine Evaluation Centers in Baylor 
and the University of Vermont. 

Spain 

An NIAID scientist was a member of the four-person 
U.S. team sent during the summer of 1981 to assist the 
Spanish Government with the investigation, manage- 
ment, and control of the toxic oil poisoning associated 
with an adulterated batch of commercial olive oil. 

Sudan 

Michigan State University has an ICIDR program 
project award to collaborate with the Ministry of Health 
on the clinical trials of new antischistosomal drugs (e.g. , 
oltipraz), the in vitro cultivation and drug-sensitivity 
testing of malarial strains from the Sudan, the ecology 
of Simulium damnosum, and the epidemiology of human 
orchocerciasis. Collaborative arrangements have been 
made with the WHO Malaria Training Center (Sennar), 



60 



USAID, Rhone Poulenc (Paris), and West German 
investigators. 

Sweden 

During FY 1981, NIAID initiated discussions with 
Swedish health authorities on bilateral epidemiological 
research opportunities in the Stockholm County Health 
Care Information System. At the present time, NIAID 
and Swedish intramural scientists are collaborating in 
two areas: with the Universities of Lund and Uppsala 
on the molecular aspects of mycoplasma-eukaryocyte 
interactions and with the University of Uppsala on the 
structural and functional relationships of bacterial 
antigens in the immune response. 

Switzerland 

NIAID intramural scientists have active collaboration 
with Swiss investigators at Basle on the immunology 
and chemotherapy of systemic mycoses and at 
Neuchatel on the natural history and public health 
significance of a previously unrecognized rickettsia in 
the Ixodes ricinus tick similar to the Rocky Mountain 
Spotted Fever agent. An investigator-initiated grant to 
the University of Zurich supports studies on the in vitro 
and in vivo specificity of virus immune t cells. 

Thailand 

The University of Illinois has an ICIDR program project 
award which involves collaboration with the Universi- 
ties of Cincinnati, New Mexico, and Chiang Mai and the 
McKean Rehabilitation Institute in four interrelated 
areas: the epidemiology and seroepidemiology of 
leprosy infection and disease; HLA genetic studies of 
susceptibility to leprosy; the immunoregulatory abnor- 
malities and immunopathology of leprosy; and pha- 
gocytic cell functions and metabolism in leprosy. 

U.S.S.R. 

NIAID's formal involvement in the U.S. -U.S.S.R. 
Agreement for Cooperation in the Fields of Medical 
Science and Public Health has been limited to influenza. 
This initiative, under the coordination of CDC, pro- 
vides for exchange of information, scientific meetings, 
visits by scientists, and a mutual exchange of virus 
strains and laboratory reagents. 

United Kingdom 

The Medical Research Council Clinical Research Centre 
(Harrow) collaborates on the electron microscopy of 
bacteria and on mycoplasma. The London School of 
Tropical Medicine and Hygiene is active in studying the 
biochemical and genetic mechanisms of obligate in- 
tracellular parasites, in the role of bacterial antigens in 
immune response, and on immune responses to 
rickettsial infections and the Legionnaire's bacterium. 
Two extramural research grants to the University of 
London deal with the regulation of immune responses 
by specific factors and the immunogenetic regulation of 
t cell-macrophage interaction. Four English scientists 
hold NIAID research training grants in diverse areas, 
including the role of complex oligosaccharides in 
nematode development. 



Venezuela 

NIAID laboratories are collaborating with the Universi- 
ty of Caracas in epidemiological, clinical, and biochemi- 
cal studies of human entero viral infection. As nine of 
the 10 priority areas in the biomedical and epidemiolo- 
gical research component of the draft U.S. -Venezuelan 
Joint Health Agreement are communicable diseases, 
Dr. Krause is serving as the interim coordinator. In July 
1981, Drs. Krause and Western visited the Pan Amer- 
ican Center for Research and Training in Tropical 
Diseases (CEPIALET), the Venezuelan Institute for 
Scientific Investigation (IVIC), the Tropical Medicine 
Institute (IMT), the Torrealba, Institute, the National 
Institute of Health (INH), and "La Trinidad" Medical 
Teaching Center to determine the present level of 
scientific exchange and opportunities for new and 
expanded collaboration. 

Zambia 

NIAID has long-standing scientific exchange with the 
Tick Diseases Unit (Lusaka) in the morphology and 
classification of African specimens. In May 1981, the 
WHO team leader of the Tropical Disease Research 
Center (Zambia) visited NIAID. 

Zimbabwe 

Following a visit to NIAID by the Secretary of the 
Ministry of Health in September 1980, NIAID has begun 
the exchange of scientific information with the Blair 
Research Institute. An NIAID Staff Fellow spent 3 
months in the Infectious Diseases Service of the 
University Hospital (Salisbury). 

Multilateral Activities 

At present, NIAID intramural laboratories serve as 
WHO Collaborating Centers in rickettsial diseases, 
mycoplasma, and respiratory viruses other than in- 
fluenza. During FY 1979, WHO designated the NIAID 
Microbiology and Infectious Diseases Program as one of 
three collaborating centers on interferon. The NIAID 
extramural program also provides indirect support to 
U.S. institutions that serve as WHO Collaborating 
Centers. Among the most active are WHO Collaborat- 
ing Centers in arboviruses (Yale), enteroviruses 
(Baylor), influenza (CDC and St. Jude Children's 
Research Hospital), and immunologv (Scripps Clinic). 
At the invitation of WHO and TDR, NIAID staff and 
awardees participated actively in meetings or expert 
panels, as consultants to WHO or member countries, or 
as faculty in WHO-sponsored training activities. NIAID 
staff are particularly active in support of the WHO 
Immunology Program, including participation in the 
annual WHO Immunology Course in Lausanne. 

Extramural Programs 

The NIAID extramural portfolio in Tropical Medicine is 
drawn from nine areas of the Microbiology and 
Infectious Disease Program (MIDP). These are: tropical 
diseases; the ICIDR and TRU Programs; general 
parasitology; tropical virology; tropical bacteriology; 
tropical mycology; rickettsiae; and vector pathogens. 
In May 1980, NIAID phased out the International 



61 



Centers for Medical Research (ICMR) program which had 
been in operation since 1960. The ICMR program had 
originally been established in the NIH Office of 
International Research under the authority of Public 
Law 86-610 (International Health Research Act of 1960) 
and was transferred to NIAID in 1968. An ICMR was a 
discrete research organization sponsored by a U.S. 
health institution to provide a stable base for research 
and training through research centers located overseas. 
Collectively, the four ICMR units in Kuala Lumpur 
(Malaysia), Dacca (Bangladesh), Lahore (Pakistan), and 
Cali (Colombia) served as a national resource to provide 
a pool of investigators in tropical diseases and to 
stimulate young scientists to pursue careers in interna- 
tional biomedical research. 

NIAID has superseded the ICMR Program with 
four award mechanisms which are intended to provide 
greater flexibility and cooperation between U.S. tropical 
medicine specialists and scientists in developing coun- 
tries. They are: the International Collaboration in 



Infectious Disease Research (ICIDR) Program; the 
Tropical Disease Research Units (TRU); the Internation- 
al Tropical Disease Research (ITDR) Fellowships; and 
the Senior International Fellowships with an emphasis 
in tropical diseases. 

The ICIDR program differs from the ICMR in 
several respects. Perhaps the most important is the 
emphasis given to developing a peer relationship 
between the U.S. institution or investigators and their 
counterparts. The program focus will be on infectious 
diseases, and at least 70 percent of the award must be 
spent overseas. The ICIDR program has two parts. 
Program project (part A) grants are for collaborative 
research in a series of related projects. Exploratory 
project (part B) grants are between individual scientists 
in a single area. The current part A and B awards 
totaling $2.6 million by principal U.S. investigators, 
cooperating institutions, and major research emphasis 
are shown below. 



NIAID International Collaboration in Infectious Disease Research (ICIDR) 
Program FY 1981 

Part A. Program Project Grants 

U.S. University/Principal Invest. 

Harvard School of Public Health 
(Dr. T.H. Weller) 

University of Illinois 
(Dr. K.C. Nelson) 

Cornell University Medical 

College 

(Dr. T.C. Jones) 

Michigan State University 
(Dr. J.F. Williams) 



Tulane School of Public Health 
(Dr. T.C. Orihel) 



Foreign Institution/Country 

Federal University of Bahia, 
Brazil 

Chiang Mai University, 

Thailand 

Federal University of Bahia, 
Brazil and University of 
Brasilia, Brazil 

Central Laboratory, Ministry 
of Health, Khartoum, Sudan 

Colciencias Cali, Colombia and 
Institut Francais d'Haiti 
Port-au-Prince, Haiti 



Research Interest 

Schistosomiasis 
Chagas' Disease 

Immunobiologv and 
Epidemiology of Leprosy 

Leishmaniasis 
Trypanosomiasis 

Schistosomiasis 

Orchocerciasis 

Malaria 

Filariasis 
Trypanosomiasis 
Leishmaniasis 
Intestinal Parasites 



Estimated Budget 

$ 295,203 

385,634 
709,601 

429,266 

487,836 



Part B. Exploratory Development 

University of Washington 
(Dr. T.M. Buchanan) 



University of South Florida 
(Dr. G.E. Rodrick) 

University of Hawaii 
(Dr. W.A. Siddiqui) 

Columbia University 
(Dr. P. D'Allessandro) 

Ohio State University 
(Dr. J.D. Briggs) 



Grants 

National School of Biological 
Sciences, National 
Polytechnic Inst., Mexico 
City, Mexico 

Fundacao Oswaldo Cruz, Rio 
de Janeiro, Brazil 

Aligarh Muslim 
University of Aligarh, India 

Federal University of Rio de 
Janeiro, Brazil 

University of Nigeria, 
Nsukka, Nigeria 



Subtotal Part A 



Leprosy 



2,307,540 
42,038 



Schistosomiasis 




25,838 


Malaria 




59,619 


Visceral 




98,166 


Leishmaniasis 






Vectors of Human 




51,367 


Disease/Malaria 


$ 




Subtotal Part B 


277,028 


Total ICIDR 


$2,584,568 



62 



NIAID Tropical Disease Research Unit (TRU) Program: FY 1981 

Robert Breck Brigham Hospital (Dr. J. David) 



Case Western Reserve University (Dr. A. Mahmoud) 



Immunology of Chagas' 
Disease, Filariasis, and 
Leishmaniasis 

Multidisciplinary in 
Parasitic Infections 
(Schistosomiasis) 

Total TRU 



466,894 



248,640 



$ 715,534 



The Laboratory of Parasitic Diseases and the Rocky 
Mountain facilities have functioned for many years as 
Federal laboratories committed to basic research in 
tropical diseases. The Yale Arboviral Research Unit 
(YARU) has, with NIAID support, provided a Universi- 
ty-based center of excellence in tropical virology. The 
NIAID-funded TRU program is designed to expand this 
network through awards to outstanding U.S. institu- 
tions for multidisciplinary research in tropical medi- 
cine. In addition to new knowledge, this program will 
provide the opportunity for institutional strengthening, 
research training for young U.S. and foreign scientists, 
career development, and a domestic counterbalance to 
the ICIDR initiative overseas. During FY 1981, the TRU 
award to the Robert Breck Brigham Hospital, Harvard 
University, continued, and ongoing support to Case 
Western Reserve was incorporated into the TRU 
program. 

The ITDR Fellowship program was initiated in 1979 
with NIAID funds to provide a limited number of 
postdoctoral fellowships for advanced training in 
tropical disease research in the U.S.A. for scientists 
from developing countries. As applications were en- 
couraged from countries without FIC/NIH nominating 
committees, the WHO regional and country offices and 
the TDR Programme have cooperated in screening 
candidates. In FY 1981, an Indian and Peruvian scientist 
completed the first two ITDR awards for research 
training in leprosy and malaria, respectively. No new 
awards were made during the fiscal year. 

The Senior International Fellowship (SIF), with an 
emphasis in tropical diseases, is a special competition 
for mid-career and senior U.S. scientists to spend 3-12 
months in cooperative research projects on tropical 
medicine outside the U.S.A. The initial three awards for 
overseas research in Kenya, The Netherlands, and the 
U.K. were carried out during FY 1981. The Fogarty 
International Center administers both the ITDR and the 
SIF/Tropical Diseases Fellowships. 

Advances in immunology have increased the 
international activities of the Immunology, Allergic and 
Immunologic Diseases Program (IAIDP). IAIDP, for 
example, supports the work of the International Bone 
Marrow Transplantation Registry maintained at the Mt. 
Sinai Medical Center in Milwaukee and the Hybridoma 
Bank at the American Tissue Culture Collection (ATCC) 
in Rockville, Maryland. IAIDP staff are active in the 
International Union of Immunological Societies (IUIS)- 
WHO Committees on Standardization. In addition to 
WHO consultant services, IAIDP participated in bilater- 



al immunology initiatives with Japan, Kuwait, and the 
People's Republic of China. 

Competing Foreign Awards 

Non-U. S. scientists may compete for NIAID grant 
awards and apply directly for "sole-source" contracts in 
any program area. In FY 1981, foreign awards totaled 
$1,146,459 and constituted 3.7 percent of the tropical 
medicine nternational research budget. Of the 27 
awards to investigators in 11 countries, however, only 
one research and three training grants ($58,355) were 
relevant to tropical medicine. No principal investigator 
came from a developing country. The 27 FY 1981 foreign 
awards represent a significant decline from the 46 
awards ($1,215,238) in FY 1980. This is due primarily to 
14 fewer training grants to English scientists. Since FY 
1979, competing foreign awards have declined nearly 10 
percent in fixed dollars. 

Reagents and Reference Material 

While the major functions of the NIAID Extramural 
Activities Program are program analysis, project re- 
view, and grant or contract management, its Research 
Resources Branch (RRB) also coordinates the Institute's 
substantial activities in providing reagents and re- 
sources without charge to investigators and govern- 
ment agencies throughout the world. During FY 1981, 
NIAID maintained 18 major grants or contracts for the 
distribution of micro-organisms, parasites, or animals 
for research which were relevant to tropical medicine. 
Additional reference materials are frequently provided 
on a less formal basis by intramural laboratories. 

During this period, NIAID also completed a 
research contract with the University of Alabama to 
determine optimal conditions for the preservation, 
retrieval, storage, and distribution of fragile bacterial 
host strains. The study has resulted in specifications for 
"Packaging, Maintaining and Distributing Bacterial 
Host Strains and Bacteriophage Vectors for Recom- 
binant DNA Research." The RRB also arranged for the 
processing and packaging of additional hypersensitiv- 
ity antigens and antisera such as short ragweed extract 
and an antibody to this extract, which will be offered to 
WHO as a reference preparation. New procurement 
contracts will also provide several other new reagents, 
including rotavirus type 2, hypersensitivity pneumoni- 
tis, and penicillin minor determinant mixture. 

RRB continues to distribute a variety of allergenic 
products for in vitro or investigational use which include 



63 



venoms of honey bees, yellow jackets, and hymenop- 
tera venom diluent. Limited contract funds, however, 
are forcing a consolidation or reduction of some 
services. American Type Culture Collection (ATCC), 
for example, is now totally responsible for the distribu- 
tion of the NIAID enterovirus, adenovirus, rhinovirus, 
and arbovirus reagent collections. While NIH scientists 
continue to receive these research reagents at no cost, 
all other U.S. and foreign investigators are required to 
pay a nominal ATCC handling fee and shipment costs. 

The NIAID intramural program now comprises 12 
research laboratories, three of which are located at the 
Rocky Mountain facilities in Hamilton, Montana. 
Although all have significant international health 
activities, the major portion of tropical medicine 
research is concentrated in the Laboratory of Parasitic 
Diseases (LPD). The Epidemiology Branch (EB) of the 
Rocky Mountain Laboratory facilities also devotes a 
substantial portion of its resources to medical zoology 
and vector studies. The Laboratory of Infectious 
Diseases (LID) is becoming increasingly involved in 
collaborative investigations on respiratory viruses, 
diarrheal diseases, and hepatitis. The apparent increase 
in intramural research to $6.5 million in FY 1981 from 
$3.6 million in last year's NIH International Report is 
due to a change in assigning costs to individual 
intramural research projects. The actual level of in- 
tramural research remained about the same. 

Recent advances in immunology and laboratory 
techniques are now being applied to diseases prevalent 
in the tropics with a consequent tendency for broader 
involvement by basic biomedical research laboratories 
in international research. The Laboratory of Microbial 
Immunology (LMI), for example, is active in studying 
the immune reaction to several parasitic infections such 
as trypanosomes, malaria, and amebae in experimental 
models. The Laboratory of Clinical Investigation (LCI) 
and the facilities at the Clinical Center are available for 
detailed studies on U.S. or foreign patients with known 
or suspected tropical diseases. 



NIAID intramural investigators collaborate with 
colleagues outside the U.S.A. in many research areas 
beyond the scope of tropical medicine in the exchange 
of data and diagnostic material or the introduction and 
standardization of laboratory techniques. Collaboration 
immediately relevant to tropical medicine also occurs 
within NIH and with other Federal agencies, particular- 
ly the Centers for Disease Control (CDC), the Office of 
Naval Research (ONR), the Walter Reed Army Institute 
of Research (WRAIR), and the Bureau of Biologies 
(BOB). 

In FY 1981, 27 intramural projects had major input 
from scientists in 18 foreign countries. England (6) was 
the most frequent collaborating country named, fol- 
lowed by Egypt (4), India (4), France (3), Japan (3), The 
Netherlands (3), and Sweden (3). The Dominican 
Republic, Israel, and Switzerland had two cooperating 
units. Argentina, Brazil, Czechoslovakia, Germany, 
Italy, the People's Republic of China, South Africa, and 
Venezuela each had one. Intramural scientists are also 
involved in the technical work of bilateral (USAID), 
multilateral (WHO, PAHO), or voluntary (Rockefeller 
Foundation, National Academy of Sciences) agencies 
concerned with tropical medicine and international 
research. The NIAID intramural program benefits 
considerably by the participation of foreign scientists 
who visit through a variety of mechanisms for periods 
of days to several years. In FY 1981, for example, NIAID 
provided funds for long-term visiting scientists from 
countries under the regular NIH Visiting Program. 

Conferences, Seminars and Meetings 

During FY 1981, NIAID made commitments to fund 22 
conferences and workshops, the majority of which 
included the participation of foreign scientists. The 
actual level of funding for conferences, however, was 
about half of what it had been during the previous 3 
fiscal years. NIAID staff also participated in a variety of 
important scientific meetings. A number were of 
particular international interest: 



•October 9-12, 1980: 
•October 27-31, 1980: 
•November 4-7, 1980: 
•November 20-21, 1980: 
•December 1-6, 1980: 

•December 17-19, 1980: 
•January 5-9, 1981: 

•January 14-16, 1981: 
•January 1981: 

•February 2, 1981: 
•March 3-4, 1981: 
•March 8-9, 1981: 

•March 9-13, 1981: 



VIII International Spores Conference 

VIII International Immunopathology Symposium 

American Society of Tropical Medicine and Hygiene 

International Workshop on Mechanisms of Local Immunity 

International Conference on the Impact of Viral Diseases on 
Developing African Countries 

International Workshop on Hepatitis A Infections 

Meeting on Molecular Biology, Pathogenicity, and 
Epidemiology of Bacterial Parasites 

Malaria Immunity and Vaccine Development Workshop 

Workshop on Potential of Human Immune Globulin for the 
Prevention and Treatment of Bacterial Disease 

Concept Review of Herpes Vaccine 

Consensus Development Conference on Reye's Syndrome 

Symposium on Current Topics in Biostatistics and 
Epidemiology 

Workshop on Genetic Variation among Influenza Viruses 



MBL 

San Diego 
Atlanta 
Bethesda 
Nairobi (Kenya) 

Athens (Greece) 

Santo Domingo 

(Dominican 

Republic) 

Bethesda 

Bethesda 

Bethesda 
Bethesda 
Bethesda 

Salt Lake City 



64 



•March 30- 
April2, 1981: 

•May 11-13, 1981: 

•May 12-13, 1981: 
•June 7-12, 1981: 

•June 17-19, 1981: 
•June 18-19, 1981: 
•July 27-31, 1981: 

•August 3-7, 1981: 
•August 2-7, 1981: 
•August 22-29, 1981: 



International Symposium on Viral Hepatitis 

Planning Workshop on Genitourinary Infections and Outcome 
of Pregnancy 

Workshop on Anti-Viral Therapy of Genital Herpes 

XIV International Leucocyte Culture Conference 

Immunoparasitology Symposium 

Serodiagnosis of Systemic Mycoses 

Conference on Bacterial Virulence and Pathogenesis 

Gordon Conference on Parasitology 
V International Congress on Virology 
International Epidemiological Association 



►September 17-19, 1981: Workshop on Infectious Diseases in the Aging 



New York City 
Bethesda 

Bethesda 

Heidelberg 
(Germany) 

Corvallis 

Bethesda 

Hamilton 
(Montana) 

Strasbourg (France) 

Edinburgh 
(Scotland) 

Bethesda 



65 



NATIONAL INSTITUTE 

OF ARTHRITIS, DIABETES, AND 

DIGESTIVE AND 

KIDNEY DISEASES 



Introduction 

The National Institute of Arthritis, Diabetes, and 
Digestive and Kidney Diseases (NIADDK) is responsi- 
ble for the conduct and support of biomedical research 
relevant to a wide range of chronic, disabling disorders. 
A number of Institute-funded research activities draw 
upon the talents and investigative expertise of the 
international scientific community. This report high- 
lights the nature and scope of collaborative and 
individual international research efforts and activities 
carried out with NIADDK support as integral parts of 
the Institute's overall mission. 

Continued collaboration with international scien- 
tists and funding of projects that may have worldwide 
impact are ongoing priorities within the NIADDK. It is 
only through these mechanisms that we can hope to 
control, prevent, and ultimately eliminate the many 
chronic and disabling disorders that fall within the 
purview of the Institute. 

Summary of NIADDK International 

Programs and 

Activities: Bilateral Agreements 

The National Institute of Arthritis, Diabetes, and 
Digestive and Kidney Diseases participates in three 
formal collaborative research programs under the 
auspices of the Bilateral Cooperative Agreement Pro- 
gram: The U.S. -Japan Malnutrition Panel Research 
Support Program, which is part of the U.S. -Japan 
Cooperative Medical Science Program administered by 
the National Institute of Allergy and Infectious Dis- 
eases; the U.S.-U.S.S.R. Cooperative Program in 
Arthritis, which had its origin in the U.S.-U.S.S.R. 
Health Exchange Program of 1972, designed to improve 
collaboration between the two countries in the field of 
public health and medical science; and the NIH- 
INSERM Agreement between the NIH and the National 
Institute of Health and Medical Research of France. 

The following sections outline current activities 
and the progress that has been achieved in these 
cooperative efforts. 

France 

Under the agreement program between the NIH and 



the National Institute of Health and Medical Research of 
France (INSERM), substantial scientific collaboration 
has occurred between the Clinical Endocrinology 
Branch of the NIADDK and the Unite de Recherche sur 
la Glande Thyroide et la Regulation Hormonale of 
INSERM. The exchange of scientists from both groups 
has provided excellent opportunities for collaborative 
research and an effective exchange of personnel in the 
study of thyroid hormone synthesis and metabolism. 

The exchange has been useful and profitable 
because the investigators from each country normally 
work on different but related aspects of thyroid 
physiology and biochemistry. By combining the pro- 
grams available to each group, new procedures have 
evolved to resolve specific problems in thyroid func- 
tion. In addition, many papers have been published 
jointly by NIH and the INSERM intramural scientists. 

A Clinical Endocrinology Branch scientist visited 
France in fiscal year 1981 to present lectures and 
collaborate with staff of the Unite de Recherche sur la 
Glande Thyroide et la Regulation Hormonale. A 
scientist of that institute visited NIH in September, and 
arrangements were made for her return to NIH for a 
year to conduct research and collaborate with NIADDK 
intramural scientists. 



Israel 

A cooperative study between investigators in the Bone 
Diseases Program, NIADDK, and members of the staff 
of Hadassah University Hospital in Jerusalem, Israel, 
involving approximately 300 ambulatory middle-age 
patients with osteoporosis, is observing the effects of 
prolonged administration of a combination of calcium, 
phosphate, and fluoride salts on bone structure and 
density. The relationship between long-term levels of 
intake of various dietary components and the preva- 
lence and severity of osteoporosis among patients with 
different ethnic backgrounds, geographic origins, and 
dietary customs provided an optimal opportunity for 
this type of study. New techniques of early diagnosis of 
osteoporosis through bone densitometry sophisticated 
enough to discern minimal changes in bone density, 
particularly in the spinal vertebrae, have been de- 
veloped. 



67 



Japan 

U.S. -Japan Cooperative Medical Sciences Program - Mal- 
nutrition Panel: The Malnutrition Panel was established 
as a part of the U.S. -Japan Cooperative Medical 
Sciences Program in 1966, and is administered by the 
Digestive Diseases and Nutrition Program of the 
NIADDK. The panel is concerned with developing 
solutions to nutritional problems of importance to 
Asian people through basic, applied, and clinical 
research. Such research has been supported by the 
NIADDK, and by the National Institute of Child Health 
and Human Development (NICHD). These studies may 
be conducted overseas, or in the U.S., as long as the 
subject of the research is pertinent to the international 
problems addressed. 

While food availability is no longer a major problem 
in most countries in Southeast Asia, a number of social, 
political, and economic forces account for serious 
inequities in food distribution, and malnutrition con- 
tinues to be one of the most serious problems in Asian 
countries, excluding Japan. The most commonly en- 
countered forms of undernutrition are protein-energy 
malnutrition, iron deficiency, and vitamin A deficiency. 
Superimposed are various disease states (particularly 
diarrheal infections) which cause impaired utilization 
and loss of nutrients. Malnutrition complicated by 
diarrheal infection is actually the primary cause of death 
in children under 5 years. Undernutrition has a severe, 
adverse effect on the outcome of pregnancy, leading to 
more premature and low birth-weight infants with 
increased disabilities and inadequate nutrient reserves. 
Iron deficiency, which is widespread, may interfere 
with immune responses, cause lowered resistance to 
infection, and reduce functional physical capacities. 
Vitamin A deficiency in turn causes many thousands of 
cases of damaged vision and total blindness in young 
children each year, especially in Indonesia. 

The Malnutrition Panel has identified as program 
objectives five areas where research effort may most 
benefit the undernourished of Asia. These are: 
•Influence of environmental and host factors on 
nutritional requirements. 

•Health significance and methods of preventing iron 
deficiency. 

•Interaction of nutrition, immune competence, and 
infection. 

•Effects of nutrition on physical and mental develop- 
ment, behavior, physical capability, and work perform- 
ance. 

•Health consequences of different (and changing) 
dietary patterns and food habits. 

During fiscal year 1981, 16 research grants were 
active which dealt with the objectives of the U.S. -Japan 
Malnutrition Panel. Funds provided amounted to $1.1 
million, almost equally divided between NIADDK and 
NICHD. 

Studies have been conducted at the University of 
Colorado involving dietary zinc supplementation in 
3-to 6-year-old children at or below the 10th percentile 
for body weight and height. It was observed that male 
children given 10 mg of oral zinc per day gained in 
height significantly more than did controls. This effect 



was not observed in female children. A marked 
improvement in appetite was also observed in those 
given the zinc supplement. These observations suggest 
that zinc supplementation may improve appetite and 
growth velocity in populations where marginal zinc 
deficiency exists. 

Studies by scientists at the Louisiana State Uni- 
versity, supported by NICHD, show that pregnant 
primates can withstand diets containing as little as 3.35 
percent protein (casein) without obvious ill effects to 
themselves. This level is well below that consumed by 
most primate populations. Moreover, the offspring 
were normal when tested by numerous physiological, 
behavioral, and growth measures, provided the babies 
were well-fed after birth. Louisiana State scientists 
concluded that most primates, probably including 
humans, may be well-adapted to withstand temporary 
lower protein intakes during pregnancy. 

In studies with malnourished children (ages 6-16 
years) supported by NICHD and conducted in Cali, 
Colombia, it was found that the total maximum oxygen 
consumption and carrying capacity was depressed as 
compared with normal controls. These and other 
similar studies suggest that adult work capacity for a 
given malnourished individual (or one whose physical 
development was limited due to chronic malnutrition 
throughout childhood) may be less than that of average 
American or Western individuals. 

Continuing studies on the nutritional suitability of 
common staple foods for child-feeding have shown that 
a diet containing wheat to provide 50 percent of the 
daily calories and 80 percent of the protein, and 
supplemented with casein to supply the remaining 20 
percent of the daily protein requirement supported 
excellent ponderal and linear growth of children, 
although plasma amino acid levels indicated that the 
amino acid lysine was still "first limiting. " A diet with 75 
percent of calories and all of the protein coming from 
wheat seemed unable to support adequate growth in 
most infants. The addition of lysine to correct the low 
lysine intake made growth adequate in all respects. 
Potatoes alone were unable to support normal growth 
in infants. It appears that the amino acid methionine 
was "first limiting" in potato protein. Four varieties of 
whole grain sorghum flour (a staple in many underde- 
veloped countries) exhibited poor protein digestibility, 
rendering them inappropriate for child-feeding. This 
work was supported by NICHD. 

Work has continued at the Massachusetts Institute 
of Technology to develop an improved method of 
assessing protein nutrition status and protein and 
amino acid requirements, using stable isotope probes 
( 13 C, 15 H, and : H) to quantify whole-body fluxes of 
indispensable amino acids and their major metabolites. 
During the past year, this group has found that protein 
ingestion results in a reduction in the rate of whole- 
body protein breakdown when a meal that provides 
adequate energy is consumed. Whole-body alanine 
synthesis appears to increase with the ingestion of 
energy-containing meals, suggesting a role for alanine 
in maintaining whole-body nitrogen economy as well as 
energy storage. Glycine metabolism, on the other hand, 



68 



does not respond to ingestion of an energy-rich meal, 
although its rate of synthesis is adaptively reduced 
when protein intake is limited. This work may ultimate- 
ly provide a better method for the precise estimation of 
amino acid requirements in individuals than has been 
available previously. 

Current plans include studies concerning environ- 
mental and host factors affecting nutritional require- 
ments of the individual. Studies are needed to quantify 
dietary requirements for essential nutrients known to 
be limiting in populations living under various ecologi- 
cal conditions, as these may be affected by age, state of 
human development, sex, and occupation. Specifically, 
research is needed to determine whether populations 
living under conditions of chronic environmental and 
physiological stress can physiologically adapt to lower 
levels of intake without undue impairment of health 
and performance. 

The Chief of the Department of Nutrition and 
Biochemistry, Institute of Public Health in Tokyo, 
visited the laboratories of a number of U.S. nutrition 
scientists, particularly those of fellow panel members, 
on behalf of the Japanese Malnutrition Panel. He 
presented a seminar at NIH on his studies of iron 
deficiency. 

Last year, the Malnutrition Panel held a workshop 
in Morioka, Japan. The topic was "The Effects of 
Nutrition on Human Growth and Development and 
Later Life and Health: Global Priority Issues." The 
workshop addressed the possible effects of nutritional 
insults to the young on their subsequent potential to 
live healthy and productive lives. 

Despite previous accomplishments, malnutrition 
continues to be a widespread problem in Asian 
countries, except for Japan. Special efforts are being 
made to increase the amount of collaboration among 
U.S. and foreign countries in this area. Until the causes 
and consequences of malnutrition are better under- 
stood, continued research is vital to the future of 
mankind. 



U.S.S.R. 

The cooperative program in arthritis had its origin in the 
U.S. -U.S.S.R. Health Exchange Program of 1972, a joint 
agreement designed to improve collaboration between 
the two countries in the field of public health and 
medical science. In September 1973, arthritis research 
became the fourth major collaborative project in the 
health sciences in this program. 

Through a series of bilateral exchanges of scientific 
personnel, the program emphasizes clinical studies of 
the treatment of rheumatoid arthritis and systemic 
lupus erythematosus. Twelve major meetings have 
been held between the members of the cooperating 
centers, and these meetings have been supplemented 
by the exchange of reprints and lecture materials, as 
well as by discussions of preliminary results and future 
projects. 

A study of the treatment of rheumatoid arthritis 
with d-penicillamine at various dose levels was com- 
pleted in June 1980 with the entry of 100 patients by 
each side; a final report for the scientific literature is in 



preparation. Following a successful, published, de- 
scriptive study of juvenile rheumatoid arthritis, a trial 
comparing hydroxychloroquinine to d-penicillamine in 
that disease was begun in August 1981. Entry of 
patients into the trial is progressing satisfactorily in both 
countries. As assessment of the results of total hip joint 
replacement with artificial joints in both countries has 
been completed, and a report is in preparation. An 
agreed-upon assessment of hand function in rheuma- 
toid arthritis is also being conducted in the two 
countries. Large data sets bearing on the diagnosis of 
scleroderma have been exchanged and are under 
discussion. 

In the more basic sciences, considerable attention 
has been devoted to collagen synthesis and degradation 
using fibroblasts in culture derived from normal 
persons and patients with scleroderma. 

The program is organized into three major areas: 
clinical studies in rheumatic disease; basic science of 
rheumatic disease; and orthopedic surgery for arthritis. 
Projects are in operation in all three. 

At the invitation of our Russian collaborators, five 
American scientists took part in and addressed the 
International Symposium on Rheumatology sponsored 
by the All-Union Scientific Rheumatology Society in 
Tbilisi in October 1980. Our orthopedic area coordinator 
received a warm welcome and, as the first American 
ever to do so, addressed an All-Soviet Congress of 
Orthopedics and Traumatology in Kiev in September 
1981. He worked for several months in the collagen 
laboratories of the University of Pittsburgh. 

Visiting Programs 

The NIADDK Intramural Program sponsors scientists 
from many countries under its visiting programs, and in 
return, intramural scientists from the Institute spend 
time visiting and collaborating in laboratories and 
clinics abroad. During the past year, scientists from 
Israel, India, Poland, Japan, China, the United King- 
dom, France, Germany, and other countries have 
worked in the intramural laboratories and clinics of the 
NIADDK. This exchange of high-caliber scientists 
across national boundaries provides vital opportunities 
for cross-fertilization of new ideas and biomedical 
techniques. It has been a mutually beneficial mechan- 
ism for many years and is expected to continue to 
provide significant scientific dividends in the future. 

Extramural Programs 

NIADDK continues to support research by scientists 
outside the United States as part of its extramural 
research program. This is done with the award of grants 
and contracts, approved through the competitive peer 
review process, to highly qualified investigators explor- 
ing problems of high priority. In fiscal year 1981, 46 
research grants were awarded to international institu- 
tions for a total of $2,086,212; 12 training grants were 
awarded for a total of $96,960; and 7 contracts were 
awarded for $648,000. The following sections deal with 
the efforts of the NIADDK extramural program areas as 
they relate to the support of international research. 



69 



In FY 1981, the Institute's Diabetes, Endocrine, and 
Metabolic Diseases Program supported approximately 37 
international research projects in the amount of $1.9 
million. Funds from the National Institute of Arthritis, 
Diabetes, and Digestive and Kidney Diseases, the 
National Institute of Allergy and Infectious Diseases, 
and the National Institute of Dental Research enabled 
scientists from all over the world to participate in the 
Workshop on the Initial Lesion of Insulin-Dependent 
Diabetes Mellitus (IDDM) held in Reston, Virginia, in 
November 1980. This workshop gave U.S. scientists 
and their colleagues from Europe the opportunity to 
exchange ideas in the area of diabetes and immunology 
in order to further knowledge regarding the involve- 
ment of the immune system in IDDM. 

The Diabetes Program is also supporting the 
forthcoming trial on the relationship between the 
degree of blood glucose control and emergence of the 
early vascular complications of insulin-dependent di- 
abetes, which should offer opportunities for interna- 
tional collaboration in several areas: 
•Between U.S. and foreign scientists in planning the 
protocol of the forthcoming study. 
•Between the NIADDK clinical trial and an ongoing 
multinational trial supported by the Kroc Foundation. 
•On the clinical trial's Policy and Procedures Advisory 
Group. 

The Kidney, Urologic, and Hematologic Program sup- 
ports five investigator-initiated research grants that are 
international in scope. A hematologic study about 
globin gene transcription is being supported at the 
University of London, England. Two urology grantees 
are collaborating with foreign scientists in France and 
West Germany, with funding being divided between 
NIADDK and foreign institutions. In France, they are 
conducting studies on steroid receptors in prostatic 
hyperplasia; in Germany, a cooperative clinical trial is 
under way to compare the surgical with the medical 
treatment for vesico-ureteral reflux in children. The 
Chronic Renal Disease Program is currently supporting 
two international grants, one in Finland to study kidney 



graft rejection, and one in Sweden that concerns the 
metabolism of proteins, fats, carbohydrates, and salt 
during continuous ambulatory peritoneal dialysis 
(CAPD) for chronic renal failure. 



Conferences, Seminars, and Meetings 

Scientific meetings with an international audience play 
a major role in scientific communication as they provide 
a forum for the exchange of research information 
among investigators from different countries and 
stimulate scientific collaboration and cross-fertilization. 
NIADDK continues to support selected conferences 
with international participation as part of its programs. 
Examples of the types of conferences supported in part 
by NIADDK in fiscal year 1981 include: 
•Sixth International Congress of Human Genetics. 
•International Conference on Peroxisomes and Glyoxi- 
somes. 

•Twelfth International Congress of Nutrition. 
•Abnormal Hemoglobins: Genetics, and Populations 
and Diseases. 

•International Workshop on Calcium and Phosphate 
Transport Across Biomembranes. 
•Seventh International Biophysics Congress. 
•International Diabetes Foundation Committee on 
Diabetes in Youth. 

•Second International Workshop on Bone and Soft 
Tissue Densitometry. 

•International Symposium on Osteoporosis. 
•International Symposium on the Contributions of 
Chemical Biology to the Biomedical Sciences. 
•Arachidonic Acid Metabolites and the Kidney. 
•Sixth International Symposium on Bioelectrochemis- 
try. 

•Thirteenth Annual International Biomaterials Sympo- 
sium. 

•International Workshop on the Initial Lesion of 
Insulin-Dependent Diabetes Mellitus. 
•International Symposium on the Brattleboro Rat. 



70 



10 



NATIONAL INSTITUTE 

OF CHILD HEALTH 

AND HUMAN DEVELOPMENT 



Introduction 

The mission of the National Institute of Child Heath and 
Human Development (NICHD) is to conduct and 
support research on the reproductive, developmental, 
and behavioral processes that determine the health of 
children, adults, families, and populations. 

The Institute's programs are based on the concepts 
that adult health and well-being are determined in part 
by episodes in early life, that human development is a 
continuous process through life, and that reproductive 
processes and the management of fertility are of major 
concern, not only to the individual, but to the whole of 
society. 

The NICHD supports research in the reproductive 
sciences to develop knowledge to enable men and 
women to regulate their fertility with methods that are 
safe, effective, and acceptable to various population 
groups, and to overcome problems of infertility. In the 
social and behavioral sciences, Institute-sponsored 
research is aimed at understanding the causes and 
consequences of population change. Research for 
mothers, children, and families is designed to advance 
knowledge of fetal development, pregnancy, and birth; 
to identify the prerequisites of optimal growth through 
infancy, childhood, and adolescence; and to contribute 
to the prevention and treatment of mental retardation. 

The pursuit of new knowledge is basic to the 
Institute's mission. The NICHD regards international 
cooperation as a catalyst for the attainment of new 
knowledge. Through a variety of mechanisms, the 
Institute has maintained and expanded its activities in 
the international exchange of scientific information. 
Activities are conducted under bilateral agreements and 
the Special Foreign Currency Program (P.L. 480), and in 
cooperation with international agencies, the NIH 
Visiting Program, and the Fogarty International Center. 

In addition, the NICHD provides direct support to 
foreign investigators through research grant and con- 
tract awards to their home institutions, and indirect 
support through awards to U.S. institutions having 
foreign components or involvement in foreign research 
investigations. 

Bilateral Agreements and Other 
Country-to-Country Activities 



Australia 

At the University of Sydney in Australia, the NICHD 
supports a study aimed at characterizing the association 
between oral contraceptives and malignant melanoma 
of the skin. The safety of oral contraceptives is of prime 
importance to users in the U.S. and to the increasing 
numbers of users throughout the world. Preliminary 
analyses suggest that the use of oral contraceptives 
(OC's) increases a woman's risk of developing malig- 
nant melanoma of the skin and that the risk further 
increases with extended use of oral contraceptives. The 
increased risk was most marked among women who 
had used OC's for 10 or more years. Still to be 
determined, however, is the extent to which other 
factors, such as skin or hair color, and the tendency to 
burn, blister, or freckle from exposure to sunlight, 
influence the relationship. 

Australian investigators working with NICHD 
grant support have recently made great strides in 
understanding the vital role in childbirth of relaxin, a 
peptide hormone. Relaxin softens and dilates the cervix 
at the time of delivery and facilitates childbirth by 
relaxing the pubic ligament. The study, using the pig as 
an animal model, has purified porcine relaxin, deter- 
mined the hormone's molecular weight (6,000 daltons), 
and defined its structure. 

India 

In accordance with the Indo-U.S. Bilateral Agreement 
dating from 1974, and in cooperation with the U.S.- 
India Subcommission on Science and Technology and 
the India Council for Medical Research, the NICHD 
staff has participated in meetings to advance collabora- 
tive research in the population sciences and in nutri- 
tion. 

During fiscal year 1981, NICHD conducted a 
training workshop in New Delhi to teach a group of 
mid-career Indian scientists the techniques involved in 
hybridizing antibody-forming cells with certain types of 
cancer cells and cloning selected hybrids, including 
developmental biology, genetics, and reproductive 
biology. 

Japan 

NICHD supports some research under the U.S. -Japan 
Cooperative Medical Sciences Program Malnutrition 
Panel. The panel is concerned with nutritional prob- 
lems of importance to Asian people. Priority areas and 



71 



activities of the panel will be found in the NIADDK 
section, since NIADDK administers the panel. 

Nigeria 

During 1981, the Director, NICHD, served on the 
Subcommittee on Biomedical Research, U.S. /Nigeria 
Joint Task Force, established under the 1980 Memoran- 
dum of Understanding, regarding the development of 
cooperative health activities between the two nations. 
In September 1981, a formal agreement was signed 
between the U.S. and Nigeria for cooperation in the 
field of health. 

The NICHD developed a plan for U.S. -Nigeria 
research collaboration in nutrition, beginning with 
workshops to develop preliminary research protocols, 
followed by workshops in the U.S. which will include 
Nigerian investigators. 

People's Republic of China 

In January 1979, the United States and the People's 
Republic of China signed an Agreement for Coopera- 
tion in Sciences and Technology. The agreement, 
containing specific allowances for cooperative activities 
in a number of scientific fields, was furthered in June 
1979 when health officials from both countries signed 
the Protocol for Cooperation in the Science and 
Technology of Medicine and Public Health. Areas of 
cooperation between the NICHD and counterparts in 
China include human genetics, public health and health 
services research, child development and nutrition, and 
reproductive physiology and family planning. 

In fiscal year 1981, NICHD staff led and partici- 
pated in delegations to China in the areas named above. 
In a November 1980 visit to China, the Director, 
NICHD, headed the human genetics group and 
participated in the group on child development and 
nutrition. In June 1981, the Director, Center for 
Population Research, NICHD, led the first delegation to 
China in the field of reproductive physiology and family 
planning techniques. This visit was concerned only 
with biomedical research, specifically reproductive 
biology and contraception. The Director of the NICDH 
Epidemiology Program, a member of the health services 
research delegation, took part in a July 1981 workshop 
in Shanghai. Of particular interest to the NICHD is the 
development of data regarding the rate of low birth- 
weight in China, reportedly to be about half the U.S. 
rate. 

In October 1980, a study tour of scientists from 
China met with NICHD intramural staff to discuss in 
utero diagnosis of genetic disorders. 

Representatives from the Chinese Academy of 
Medical Sciences visited the U.S. between January and 
March 1981 as guests of the Institute and under the 
auspices of the human genetics portion of the U.S.-PRC 
Protocol. They met with NIH scientists and with 
physicians and researchers across the country. 

Programs of cooperation are being developed in 
many areas, and future commitments consist of con- 
tinuing discussions and the exchange of information. 

Poland 

The Fifth Annual U.S./Polish Medical Week, held 
during October and November 1980 in Bethesda, was 



hosted by the NICHD and focused on pediatrics. The 
visiting delegation was led by representatives from the 
National Research Institute for Mother and Child, 
Warsaw, and included pediatricians from various 
institutions in Poland. 

Highlights of the week included grand rounds on 
"Screening Programs for Inborn Errors of Metabolism in 
Poland," given by the leader of the Polish delegation 
and, in cooperation with the Fogarty International 
Center, a seminar on metabolic and other genetic 
disorders sponsored by the NICHD. The Polish visitors 
also attended the 50th Anniversary National Meeting of 
the American Academy of Pediatrics, which provided 
the visitors an opportunity for contact with the wider 
U.S. pediatric community. 

The NICHD and Polish representatives agreed to 
continue the exchange of information and to identify 
common research interests and areas needing further 
exploration. 

Cooperation with International 
Organizations 

World Health Organization. Members of NICHD staff 
serve as consultants to the WHO Special Programme of 
Research, Development and Research Training in 
Human Reproduction and as members of the WHO 
Committee on Resources for Research about human 
reproduction. The NICHD has also provided for the 
biological testing for long-acting contraceptive drugs 
synthesized by the WHO contractors. 

Pan American Health Organization. Supported by the 
NICHD, PAHO is studying the effects of opsonin 
replacement in Guatemalan children with severe mal- 
nutrition. Opsonins are special antibodies that coat the 
cell walls of invading bacteria to bring about their 
destruction by phagocytic white blood cells. The 
stimulus for this research stems from the observation of 
depressed opsonization of bacteria in protein-calorie 
malnutrition. This opsonin deficiency may play a role in 
the high incidence of fatal gram-negative septicemia in 
malnourished individuals. 

European Medical Research Council. Staff of the 
NICHD are members of the Council's Advisory Sub- 
group on Reproduction, which was established to 
identify areas of cooperation within Europe and 
between Europe and the United States on research in 
reproduction. The subgroup also interacts with the 
pharmaceutical industry to obtain information about 
the industry's research projects that might have a 
bearing on human reproduction. 

The NIH Visiting Program and the NICHD Intramural 
Program. The NIH Visiting Program provides opportu- 
nities for recent postdoctoral fellows and senior scien- 
tists from abroad to train and to conduct research in the 
U.S. More than 50 foreign nationals from a dozen 
countries were involved in the NICHD Intramural 
Research Program during 1981. 

NICHD intramural scientists engage in interna- 
tional collaboration in research projects relevant to their 
own work at the NIH. For example, studies in this 
country have shown large doses of vitamin E to be 
protective against blood cell damage and/or anemia in 



72 



patients with certain rare genetic metabolic disorders. 
In collaboration with the NICHD intramural staff, 
scientists in Greece have shown that vitamin E 
significantly reduces the rate of red blood cell destruc- 
tion in patients with mild anemia from an enzyme 
deficiency prevalent in the Mediterranean region 
(Mediterranean G6PD or glucose-6-phosphate dehy- 
drogenase deficiency). Although the vitamin does not 
correct the underlying defect, the administration of 
vitamin E does correct the anemia and also reduces the 
patient's vulnerability to infection. Still to be deter- 
mined is whether the protection offered by the therapy 
is sufficient to overcome the severe anemia brought on 
by drugs or infection. 

Extramural Programs 

Components of the NICHD extramural research pro- 
gram are the Center for Population Research, the 
Center for Research for Mothers and Children, and the 
Epidemiology and Biometry Research Program. 

The Center for Population Research is responsible for 
the primary Federal research effort in the population 
sciences. Included are studies on human fertility and 
infertility, the development and evaluation of methods 
of fertility regulation, and the social and behavioral 
aspects of these problems in relation to individuals and 
to populations. Through research grants and contracts, 
the NICHD supports investigators around the world. 

In Taiwan, for example, a study of fertility and 
family planning is examining the demographic transi- 
tion in that country, assessing the extent and tempo of 
fertility decline. Particular attention is given to changes 
in fertility due to changes in patterns of marriage and 
changes of family planning within marriage. The study 
has found that despite the widespread use of contracep- 
tives, the decline of the birth rate in Taiwan is probably 
being slowed because traditional familial forms and 
relationships are still very important there. 

As an indication of the relation between the 
traditional familial elements and reproductive patterns, 
the study has found that the length of time a couple 
lives with the husband's parents, the importance 
attached to having a male heir, and the expectation of 
some day living with married sons are all related to 
lower age at marriage, a large number of births, a higher 
preferred number of children, and fewer couples using 
contraception to space their children. 

The Center for Research for Mothers and Children 
(CRMC) supports biomedical and behavioral research 
aimed at making possible pregnancies and births that 
produce sound infants who can grow to adulthood free 
of disease and disability. Since its inception, the NICHD 
has promoted research on the role played by nutrition 
in the prevention of disease and disability as part of the 
strategy for achieving that goal. 

Current world food policies are largely based on 
the assumption that if most of the energy needs of 
humans are satisfied by common staple foods, protein 
requirements will also be met. This may well be true for 
adults, but investigators supported by an NICHD grant 
have shown that this assumption is not true during late 



infancy and early childhood in children in Peru. 

Bulkiness of staple foods limits amounts that can be 
consumed. Low protein content and poor digestibility 
may also limit the amount of utilizable protein available 
from such diets. For example, when 66 percent of 
calories is supplied as oats, and oats account for all 
dietary protein, then weight gain and nitrogen reten- 
tion are found to be less than when only 22 percent of 
calories and 50 percent of dietary protein are provided 
by oats. 

Investigators working on this project found a 
progressive increase in calories, carbohydrate, fat, and 
nitrogen expelled in the stools when oats supplied 44 
percent or more of dietary calories. Results of such 
NICHD research should influence nutritional programs 
for infants and children in developing countries. 

In addition to the opsonin study cited earlier, the 
NICHD is currently funding another project in Guate- 
mala to study the relationship between iron-deficiency 
anemia and behavior in infants. To date, 68 babies 
between 6 months and 2 years of age, with and without 
iron-deficiency anemia, have been tested with the 
Bayley Scales of Infant Development. Both the index of 
mental development and the index of psychomotor 
development of the anemic group were significantly 
lower than those of the nonanemic group. 

The investigators also found that in a double-blind, 
randomized clinical trial, oral iron therapy for 6 to 8 
days did not significantly improve the deficient scores 
of the anemic children. 

A group of investigators in Canada is working on a 
grant from the NICHD to discover new growth factors. 
Recently, they have found that the human pituitary 
gland contains a growth-promoting protein in addition 
to human growth hormone (hGH). The new growth 
factor appears to be a large protein (40-60,000 daltons) 
which stimulates rabbit fetal cartilage cells (chondro- 
cytes) to grow in tissue culture. This new growth factor 
has been named the "pituitary chondrocyte growth 
factor." 

The same Canadian group has also discovered the 
presence of a growth factor in the cell fluid (cytosol) of 
specimens of human breast cancer. The factor appears 
to be a protein which is found in approximately 50 
percent of breast cancer specimens, and has been 
named the "mammary tumor growth factor." This 
discovery may further the understanding of the cause of 
the rapid, uncontrolled growth that is seen in many 
forms of cancer. 

The CRMC also supports studies on the human 
learning process and communicative disorders, espe- 
cially reading disorders. Compared with speech, read- 
ing is not universal. On a worldwide basis, reading is 
relatively rare; it comes second to speech in the 
development of the individual, and requires extensive 
formal instruction. Therefore, information processing 
in reading depends on the educational methods used to 
teach reading, and on the particular properties of the 
language and orthography. NICHD-supported investi- 
gators in Yugoslavia are exploiting the special language 
situation provided by Serbo-Croatian as a means of 
probing the visual and auditory processing of language 



73 



and of comparing the processing of Serbo-Croatian to 
English. 

The Epidemiology and Biometry Research Program is 
collaborating with the Department of Epidemiology at 
Ben Gurion University, Beer Sheva, Israel, in a study of 
the effects of westernization on infant feeding practices 
among Bedouin populations who are undergoing 
transition from a nomadic to a more settled lifestyle. 
Data are being developed to test the thesis that as this 
transition takes place, infant feeding practices shift 
from long-duration breast-feeding to a combination 
breast- and bottle-feeding and/or to bottle-feeding 
exclusively. The effects of these changes on the health 
of the infants during the first year of life are also under 
study. 



Conferences, Seminars, and Meetings 

The Second Indo-U.S. Workshop on Reproduction and 
Contraception Research was held at NIH in June 1981. 
Convened in cooperation with the Indo-U.S. Subcom- 
mission on Science and Technology and the Indian 
Council of Medical Research, the workshop was an 
intensive working session. In addition to updating 
various projects previously identified in 1979 at the first 
meeting in New Delhi, topics for future collaboration 
were discussed. These areas include the development 
and testing of new contraceptives and strengthening of 
capabilities for research in clinical epidemiology, thus 
broadening the scope of cooperative efforts in repro- 
ductive biology. 



74 



11 



NATIONAL INSTITUTE 
OF DENTAL RESEARCH 



Introduction 

Although rarely fatal, dental diseases are universal and 
cause untold misery throughout the world. Aware of 
the severity of the dental problems that plague people 
everywhere, the National Institute of Dental Research 
(NIDR) collaborates with international organizations 
and institutions to stimulate and support dental 
research and to offer research opportunities to foreign 
scientists to engage in studies at the Institute's labor- 
atories in Bethesda, Maryland. 

Through international scientific cooperation and 
participation in organizations such as the Federation 
Dentaire Internationale (FDI), International Association 
for Dental Research (IADR), Pan American Health 
Organization, and the European Organization for 
Caries Research, the NIDR continues to work to lower 
the barriers to communication in the field of dental 
research and to advance dental health everywhere. 

The Institute encourages wide exchange of scien- 
tific information. NIDR Abstracts informs dental investi- 
gators of current developments in special areas of 
interest. This publication is distributed to more than 150 
foreign colleagues. Dental scientists around the world 
have been asked to register their research projects with 
the Smithsonian Science Information Exchange, and in 
cooperation with the Exchange, the NIDR annually 
publishes Dental Research in the United States and Other 
Countries. 

Summary of Bid International 
Programs and Activities 

Bilateral Agreements and Other Country-to-Country 
Activities 

Under the auspices of the recently signed agreement on 
health between the United States and Nigeria, the 
NIDR is exploring possible collaborative dental research 
projects. 

Activities with International Agencies 

The Director serves as a member of the Oral Health 
Research Advisory Group of the World Health Orga- 
nization. The Special Assistant to the Director, NIDR, 
served as a consultant to the USPHS/WHO Internation- 
al Collaborative Study of Dental Manpower Systems in 
Relation to Oral Health Status (a project officially 
transferred to the National Center for Health Services 



Research) and served as project officer for the Polish 
replication of that study, which is administered through 
the Health Resources Administration. The Special 
Assistant to the Director also served as chairperson for 
the International Relations Committee of the IADR, and 
was engaged in projects concerned with the develop- 
ment of dental research capacity in the Third World. 
NIDR participated in activities of the WHO in Switzer- 
land in connection with the Dental Health Unit and 
with the Oral Health Research Activity. 

NIH Visiting Program 

The Institute's intramural program supported or spon- 
sored 28 foreign fellows, 6 visiting associates, and 7 
foreign scientists in Bethesda. 

Extramural Programs 

During FY 1981, the Institute funded 10 foreign grants 
in the research areas of dental caries, pain control, 
craniofacial anomalies, and oral soft tissue diseases. 
Two research fellowships were supported abroad, one 
in Canada on pain control and one in Denmark on 
Langerhans cells and oral cancer. 

International collaboration during the year con- 
tinued or was initiated between NIDR scientists and 
researchers at the following institutions by means of 
grant support: 

•University of New South Wales and the Institute of 
Dental Research, Sydney, Australia (surface structure 
of oral bacteria). 

•University of Queensland, Australia (surface composi- 
tion of apatites). 

•McGill University, Montreal, Canada (lysosomes in 
amelogenesis). 

•University of Toronto, Canada (brain stem mechan- 
isms and dental pain-trigeminal nucleus caudalis). 
•College de France, Paris (migration and differentiation 
of neural crest cells). 

•Gothenburg University, Sweden (plaque control heal- 
ing after periodontal surgery). 

•University of Geneva, Switzerland (revision of the FDI 
dental lexicon). 

Conferences, Seminars, and Meetings 

In 1981, 23 NIDR scientists attended and contributed to 
such foreign meetings as the International Congress on 



75 



Thrombosis and Haemostasis, Canada; the annual Intramural Programs and Activities 

meeting of the Federation Dentaire Internationale, The microbial systematics section of the Institute 

Brazil; the World Congress on Pain, Scotland; the collaborated with the American Type Culture Collec- 

International Symposium on Glycoconjugates and the tion, the Center for Disease Control, the Food and Drug 

Proteoglycan Workshop, Japan; the European and Administration, the Veterans Administration, the 

Scandinavian Division of the International Association National Oceanic and Atmospheric Administration, 

for Dental Research, The Netherlands; the International and numerous researchers in foreign counterpart 

Working Group on Mycobacterium Taxonomy, France; organizations to establish a worldwide data bank for 

and the South African Division of the IADR, South information on the diverse strains of human oral 

Africa. The extramural program helped to support an microbiota. In addition, NIDR has cooperated with the 

international biomaterials symposium held in New World Federation of Culture Collections to train 

York State. microbiologists in developing nations to use computer- 
compatible methods of data recording. 



76 



12 



NATIONAL INSTITUTE 

OF GENERAL 

MEDICAL SCIENCES 



Introduction 

The National Institute of General Medical Sciences 
(NIGMS) supports research and research training in 
basic biomedical fields that undergird disease-specific 
initiatives of other NIH Institutes. The Institute has 
supported a number of basic research project grants in 
six different countries through three of its program 
areas. Furthermore, although it is not anticipated that 
NIGMS would set aside funds for international activi- 
ties in the immediate future, the Institute is ever alert to 
consider international cooperative projects which 
might develop and appear to be within its mission, on a 
case-by-case basis. 

Summary of International Programs 
and Activities 

Regular Research Grants 

The Institute accepts grant applications that fall within 



its mission of support of basic biomedical research from 
principal investigators at appropriate institutions in 
foreign countries. Seventeen such grants were awarded 
during FY 1981 to principal investigators in six countries 
(Argentina, Australia, Canada, Israel, Spain, and the 
United Kingdom). These awards were made in the 
Cellular and Molecular Basis of Disease Program, the 
Genetics Program, and the Pharmacological Sciences 
Program areas and totaled approximately $750,000. 

Conferences, Seminars, and Meetings 

NIGMS, as the lead Institute, joined other Institutes at 
NIH to supply foreign travel funds for American 
scientists to participate in the Sixth International 
Congress of Human Genetics which was held in 
Jerusalem, Israel, from September 13 to 18, 1981. 



77 



13 



NATIONAL INSTITUTE 
OF ENVIRONMENTAL HEALTH 

SCIENCES 



Introduction 

The post-World War II growth in industrial and 
commercial activities and the acceleration of indus- 
trialization in developing countries have shown that 
while technology has produced tremendous benefits 
for society, it has also had serious, often unanticipated 
side effects. Concern for the potentially adverse effects 
of environmental chemicals on human health and the 
ecosystem has become worldwide. The National Insti- 
tute of Environmental Health Sciences (NIEHS) serves 
as the principal Federal agency for biomedical research 
on the effects of chemical, physical, and biological 
environmental agents on human health. The research 
aims of NIEHS focus on identifying and investigating 
environmental factors that may have deleterious effects 
on human health (e.g., mutations, cancer, lung disease, 
birth defects), on quantifying these effects, on under- 
standing the mechanisms of action of toxic agents on 
biological systems, and on developing test methods for 
predicting the toxicity of chemicals. Through the 
development of these efforts, NIEHS research provides 
the basic information necessary for establishing disease 
prevention programs. These goals transcend national 
boundaries, and NIEHS plays a leading role in the 
organization and development of international efforts 
dealing with environmental health problems. 

Summary of Bid International 
Programs and Activities: Bilateral 
Agreements and Other 
Country-to-Country Activities 

Egypt 

Cooperation between American and Egyptian environ- 
mental health scientists is being carried out under the 
auspices of the U.S. -Egypt Joint Working Group on 
Health Cooperation (JWGHC). NIEHS has been 
assigned responsibility for the U.S. Subcommittee on 
Environmental and Occupational Health of the 
JWGHC. 

Efforts to date have consisted of a workshop held in 
Egypt in early 1980 to identify the biomedical impacts of 
technology transfer. During 1981, an Egyptian coordi- 
nator for this agreement visited the U.S. to discuss 
proposals for a series of workshops to be held in Egypt 
in 1982. These workshops will focus on the following 



areas: pesticides, trace metals, radiation, environmen- 
tal management, and mutagenesis. 

An information unit for environmental impact 
assessment is also being established. This project is 
directed to the needs expressed by the Egyptians for 
information in the areas of environmental and occupa- 
tional health. An Oversight Committee will be estab- 
lished to maximize the beneficial effects and to 
minimize or avoid the potential deleterious effects of 
technology transfer between the United States and the 
Arab Republic of Egypt. 

The Oversight Committee will provide the admin- 
istrative and staff functions to prepare technology 
assessment statements and develop data on the poten- 
tial health, social, biological, and environmental aspects 
of the transfer of specific items of technology relevant to 
the Egyptian people and their environment. The 
committee will also examine and describe advantages 
and disadvantages of alternative technologies eligible 
for transfer. 

These activities are funded largely through Special 
Foreign Currency (P.L. 480) Programs. 

Italy 

Cooperation between American and Italian environ- 
mental health scientists is being carried out under the 
joint U.S. -Italy Memorandum of Understanding signed 
by the Secretary, DHEW, and the Italian Minister of 
Health in 1977. Since that time, there have been several 
exchange visits by scientists from both sides and 
discussions aimed at defining areas of joint coopera- 
tion. Under discussion are possible collaborative activi- 
ties concerned with the following subjects: mutageni- 
city testing; testing of complex mixtures; long-term 
testing; and quantitative risk assessment. 

In addition to these activities, NIEHS staff have 
been involved in meetings and consultations concerned 
with the explosion of a chemical reactor in Seveso, Italy, 
which resulted in exposure of a large population to 
dioxins. 

Japan 

Cooperation between American and Japanese scientists 
on environmental health problems takes place under 
two formal agreements: the U.S. -Japan Cooperative 
Medical Sciences Program and the Agreement on 
U.S. -Japan Cooperation in Research and Development 
in Science and Technology. 



79 



Under the U.S. -Japan Cooperative Medical Scien- 
ces Program, American environmental health scientists 
participate in the Panel on Environmental Mutagenesis 
and Carcinogenesis chaired by the Associate Director 
for Genetics, NIEHS. Joint areas of research focus on the 
detection of mutagenic and carcinogenic chemicals 
using both in vitro and in vivo test systems, and on 
monitoring human populations for evidence of expo- 
sure to mutagenic and carcinogenic chemicals. Joint 
research on carcinogens and mutagens in the diet and 
dietary tract have been particularly productive. 

The 10th Joint Meeting of the U.S. and Japan was 
held in Kyoto, Japan, in September 1981, and reviewed 
the information presented at the Third International 
Conference on Environmental Mutagens, held in 
Tokyo, September 1981. 

Under the U.S. -Japan Agreement on Cooperation 
in Research and Development in Science and Technolo- 
gy, NIEHS participates in the toxicology program area 
in the counterpart working group on health. Explora- 
tory discussions on cooperation in this program were 
initiated in 1980 by an exchange of scientists for the 
purpose of familiarization with the organizations and 
research programs in this area. In September 1981, the 
Director, NIEHS, led the U.S. counterpart working 
group on health at the first meeting of the Joint 
Committee for the U.S. -Japan Cooperation in Research 
and Development in Science and Technology, held in 
Tokyo, Japan. In the toxicology program area, discus- 
sions centered on cooperation in the following subjects: 
development and validation of short-term test methods 
to detect carcinogens and mutagens; development of 
methods to test volatile chemicals; development of 
methods to study mixtures of chemicals; studies on the 
chemical initiation and promotion of cancer; and the 
development of approaches to quantitative risk assess- 
ment. 

In addition to these activities, the Director, Biomet- 
ry and Risk Assessment Program, NIEHS, continues his 
collaboration with the Radiation Effects Research 
Foundation, Hiroshima, to analyze the long-term 
health effects of atomic bomb victims. 

People's Republic of China 

Cooperation between the United States and the Peo- 
ple's Republic of China in the area of environmental 
health was initiated during 1980 under the U.S.-PRC 
Agreement for Cooperation in the Science and Technol- 
ogy of Medicine and Public Health. NIEHS is a 
participant in the public health and health services 
research, which includes concerns relating to environ- 
mental and occupational health. 

Exploratory discussions during a visit to the United 
States by the Chinese coordinator for this topic centered 
on cooperation in the following areas: biochemical and 
epidemiological research related to asbestosis and 
silicosis; biochemical and epidemiological research 
related to pesticides; development and validation of 
short-term test methods to detect and assess carcin- 
ogens, mutagens, and teratogens in the environment; 
the application of standard toxicological test methods 
and the extrapolation of laboratory animal data to man; 
the application of modern methodology to the estab- 



lishment of industrial hygiene standards, particularly in 
the coal industry; and the application of modern 
methodology to the establishment of pollution stan- 
dards for the general environment. 

During 1980-81, an NIEHS/NIOSH delegation 
visited China to participate in the Meeting of the Second 
Session of the U.S.-PRC Joint Health Committee and to 
exchange information on heavy metal toxicology, 
occupational lung disease, and the status of in vitro 
testing for carcinogenesis in the U.S. 

U.S.S.R. 

The National Institute of Environmental Health Scien- 
ces cooperates with counterpart institutions in the 
Soviet Union under two formal agreements: the 
U.S. -U.S.S.R. Medical Science and Public Health Coop- 
erative Agreement and the U.S. -U.S.S.R. Agreement 
on Cooperation in the Field of Environmental Protec- 
tion. 

Under the U.S. -U.S.S.R. Medical Science and 
Public Health Cooperative Agreement, NIEHS is the 
lead U.S. agency for the environmental health priority 
area. Formal collaboration in environmental health 
research between the United States and the Soviet 
Union is in its ninth year. The first year was concerned 
largely with establishing working relationships and 
agreeing on areas of joint study. Cooperative research 
efforts initiated in the second year involved exchange 
visits by scientists of both countries. Research results 
developed during the second and third years of 
collaboration were presented by American and Soviet 
scientists in the First Joint Symposium in Riga, Latvia, 
in December 1974. Scientific results from cooperative 
research during 1975 and 1976 were presented at the 
Second Joint Symposium, held in Marineland, Florida, 
in December 1976, and results of research conducted 
between 1977 and 1979 were presented at the Third 
Joint Symposium held in Suzdal, U.S.S.R., in October 
1979. The proceedings of these symposia were pub- 
lished in both countries. During 1977, 1978, 1979, and 
1981, major workshops were held on the following 
topics: developmental toxicology (Leningrad, Novem- 
ber 1977); biological effects of metals (Cincinnati, 
February 1978); behavioral toxicology (Suzdal, Novem- 
ber 1978); and biological effects of physical factors in the 
environment (Seattle, June 1979; and Kiev, May 1981). 

Over 50 scientific papers have been published by 
American and Soviet scientists on the results of 
environmental health research conducted under this 
agreement. In addition, a Russian-English Glossary of 
Environmental Health Terminology was published in both 
countries to assist communications between scientists. 

During 1980-81, exchange visits between Soviet 
and American scientists under the Health Agreement 
were conducted in research areas concerned with the 
biological effects of microwave and low-frequency 
electromagnetic radiation. 

NIEHS also participates in the U.S. -U.S.S.R. 
Agreement on Cooperation in the Field of Environmen- 
tal Protection, which is administered for the United 
States by the Environmental Protection Agency. The 
Director, NIEHS, serves as DHHS representative to the 



80 



Environmental Protection Agreement and cochairman 
of the working group concerned with the biological and 
genetic effects of pollution. During 1980-81, exchange 
visits under this agreement were conducted in research 
are concerned with the health effects of oil shale 
technology and the mutagenicity of environmental 
contaminants. In the area of mutagenesis, joint studies 
are being conducted to determine the significance of an 
increased mutation rate among congenitally malformed 
children in the U.S.S.R. 

Activities with International Agencies 

World Health Organization 

NIEHS staff have been active participants in programs 
of the World Health Organization (WHO) for a number 
of years. In 1975, NIEHS was designated as a WHO 
Collaborating Center for Environmental Health Effects. 
During 1980-81, the Institute, under the leadership of 
the Associate Director for Health Hazard Assessment, 
continued to provide advice and scientific expertise to 
WHO Headquarters and WHO Regional Offices. Col- 
laboration focused mainly on review of draft documents 
on new WHO guidelines for drinking water quality, 
and assessment of human exposure to environmental 
agents. 

In 1979, WHO established the International Pro- 
gramme on Chemical Safety (IPCS), a cooperative 
undertaking involving WHO, the United Nations 
Environmental Programme, the International Labor 
Organization, and their member states. During 1980, 
NIEHS assumed the function of lead institution within 
the IPCS for mutagenicity, effects on selected organ 
systems, and toxicology of selected chemicals. The 
objectives of the IPCS are to encourage international 
cooperation in the evaluations of the effects of chemi- 
cals on human health and on the quality of the 
environment; to coordinate chemical testing and toxico- 
logical research to eliminate unnecessary duplication of 
effort; to develop international protocols for laboratory 
testing, epidemiological studies, and risk asessment; to 
develop international guidelines and exposure limits 
for chemicals in air, water, and food and limits for 
hazardous chemicals in workplaces; to develop re- 
sponse mechanisms for coping with chemical emergen- 
cies which may be international in scope; and to 
promote training and development of manpower in 
areas and specialties necessary for the achievement of 
program goals. 

The IPCS Advisory Committee met for the second 
time in December 1980, again under the chairmanship 
of the Director, NIEHS. The second session of the IPCS 
Technical Committee, consisting of all the directors of 
IPCS lead institutions or their representatives, was held 
in Geneva in February. In October 1980, a cooperative 
agreement was signed between NIEHS and WHO, to 
include such activities as international evaluations of 
biological effects of chemicals and health hazard 
assessments, and review and/or validation of methods 
for testing of mutagenicity, carcinogenicity, neurobeha- 
vioral toxicity, and toxicity to reproductive function. In 
September 1981, the agreement was extended for 
another year. In order to assist NIEHS participation in 



the IPCS, a WHO Interregional Research Unit was 
established at NIEHS in 1981. 

Within the framework of IPCS, NIEHS' Office of 
Health Hazard Assessment is responsible for three 
projects: preparation of a draft document on biological 
effects of 2,6-toluene diamine; preparation of a similar 
document on phthalic acid esters; and scientific editing 
and updating of the second volume of a WHO 
monograph on Principles and Methods for Evaluating 
the Toxicity of Chemicals. Also, within the framework 
of IPCS, NIEHS staff participated in and chaired several 
planning meetings, held in Geneva during 1981, to 
develop international protocols for testing for 
mutagenicity, neurobehavioral toxicity, and reproduc- 
tive toxicity. 

NIEHS staff also participated in a Workshop on 
Methods for Assessing the Effects of Chemicals on 
Reproductive Functions, organized by the Scientific 
Group on Methodologies for the Safety Evaluation of 
Chemicals (SGOMSEC) in May 1981 in Ispra, Italy. 
SGOMSEC is one of the IPCS projects implemented in 
collaboration with the Scientific Committee on Prob- 
lems of the Environment of the International Council of 
Scientific Unions (SCOPE/ICSU) in May 1981. 

In other WHO activities, the Chief of the Labora- 
tory of Reproductive and Developmental Toxicology 
continued his role as temporary adviser to the Toxicolo- 
gy Review Panel of the WHO Special Programme of 
Research, Development, and Research Training in 
Human Reproduction. The review panel meets twice a 
year to consider the potential toxicity associated with 
current and future approaches to contraception. An 
NIEHS Visiting Scientist served as a WHO temporary 
adviser in Geneva to assist in the final scientific editing 
of the environmental health criteria document on 
arsenic. The Associate Director for Genetics, and the 
Head, Environmental Mutagenesis Test Development 
Program, participated in the WHO Consultation on 
Genetic Monitoring for Environmental Effects, Ottawa, 
Canada, October 17, 1980. The purpose of the consulta- 
tion was to discuss how to evaluate effects of exposure 
of individuals in the human population to mutagens. 

Health Scientist Exchange Programs and NIH 
Visiting Program 

During 1980-81, collaborative research activities were 
carried out in the intramural laboratories by 53 Visiting 
Fellows and Scientists. They came from Australia, 
Belgium, Canada, England, Finland, France, Hungary, 
India, Japan, Korea, New Zealand, People's Republic of 
China, Sweden, Switzerland, Taiwan, West Germany, 
and Yugoslavia. 

Collaborative research projects included studies 
on: mutagenicity test methods; biometry and quantita- 
tive risk assessment; mechanisms of carcinogenicity; 
pharmacokinetics and liver metabolism; neurobeha- 
vioral, pulmonary, and reproductive toxicity; and the 
effects of noise and physical factors on the nervous 
system. 

Two WHO fellows from the People's Republic of 
China are currently receiving training in the Institute's 
Laboratory of Pulmonary Function and Toxicology. 



81 



Extramural Programs 

Through its extramural program, NIEHS provides 
support to the State University of Leiden, The Nether- 
lands, to study the induction of genetic damage by 
chemical mutagens; the University of Western Ontario, 
London, Canada, to study the nature of lead-binding 
and mercury-binding nuclear proteins; the University 
of Turku, Finland, to study gastrointestinal and pul- 
monary metabolic functions; the State Agricultural 
University, Wageningen, The Netherlands, to study 
chemically induced nondisjunction in mutant mice; and 
Tel Aviv University, Israel, to study hydrocarbon 
recognition in petroleum-degrading bacteria. 

Conferences, Seminars, and Meetings 

In order to provide an opportunity for scientists from 

different countries to exchange research results and 

stimulate scientific collaboration, NIEHS continues to 

support a number of conferences with international 

participation as part of its programs. Examples of the 

types of conferences supported in part by NIEHS this 

past year include: 

•Symposium on Molecular and Cellular Mechanisms of 

Mutagenicity. 

•Statistical Analysis of In Vitro Test for Mutagenicity. 

•Conference on Phthalates. 

•Symposium on Lung Neuroendocrine Cells and 

Regulatory Peptides. 

•Target Organ Toxicity: Immune System. 

•International Lead Conference on the Effects of Lead 

Exposure on the Behavior of Children. 

Intramural Programs and Activities 

NIEHS scientists, from various intramural laboratories 
continue to collaborate on an informal basis with 
scientists from a number of nations. The Chief, 
Comparative Medicine Branch, continues to be a 
charter member of the International Committee on the 
Wasting Marmoset Syndrome (WMS). The committee 
was chartered in 1978 by the Division of Research 
Resources of NIH, and includes participants from 
Australia, Brazil, The Netherlands, Peru, the United 
Kingdom, the U.S., and the U.S.S.R. The WMS bears 
resemblance to protein-calorie deficiency in man, and 
the current focus of attention is on a nutrition causation. 

The Chief, Laboratory of Biochemical Genetics, 
serves as a committee member of the International 
Commission for the Protection Against Environmental 
Mutagens. Two NIEHS scientists participated in a Latin 
American Course on Genetic Toxicology which was 
held in Mexico City, Mexico, in August 1981, for the 
purposes of developing new methods of identifying 
potential mutagens and carcinogens; offering a compre- 
hensive and balanced view of the field of genetic 
toxicology; stimulating multidisciplinary investigation 
of the effects of environmental contamination; and 
defining particular strategies for the study of environ- 
mental problems in Latin America. 

Laboratory of Environmental Biophysics scientists 
participated in the International Symposium of Spin 



Trapping and Nitroxyl Radical Chemistry at the Uni- 
versity of Guelph, Canada, July 16, 1981. In June 1981, 
NIEHS also collaborated with the University of Buenos 
Aires, Argentina, on the free radical metabolism of 
nifurtimox, a nitrofuran used in the treatment of 
Chagas' disease. 

The Chief, Laboratory of Environmental Chemis- 
try, participated in a Workshop on Dioxins and Related 
Compounds in Rome, Italy, October 1980. Two NIEHS 
scientists are also collaborating with the Department of 
Pharmacology, University of Urbino, Italy, on the 
development of a radioimmunoassay capability for 
dioxins applicable to the Seveso, Italy, dioxin con- 
tamination problem. This methodology, developed in 
NIEHS laboratories, is under consideration for adop- 
tion by the American Society for Testing and Materials 
as a standard method. Another NIEHS scientist was 
invited to give the plenary lecture to the British Society 
of Mass Spectrometry in Cambridge, England, Septem- 
ber 1981. Collaborative research efforts, which are 
determining the stereoselectivity of the enzymatic 
reaction between glutathione and styrene oxide, con- 
tinued between the Laboratory of Pharmacology and 
Hebrew University, Israel. NIEHS is also collaborating 
with Hebrew University on the toxicity and metabolism 
of the trichothecene mycotoxin, T-2 toxin. A Laboratory 
of Pharmacology scientist is continuing his collabora- 
tive research efforts with scientists at the Medical 
School in Dundee, Scotland, in which the effects of 
hormone administration on the perinatal development 
of xenobiotic-metabolizing enzyme systems are being 
studied. 

Collaborative research is continuing between the 
Laboratory of Reproductive and Developmental Toxi- 
cology and the Institute of Pharmacology and Toxicolo- 
gy, University of Wurzburg, Federal Republic of 
Germany. Scientists in both institutions are studying 
the target organ metabolism and bioactivation of the 
carcinogenic estrogen, diethylstilbestrol (DES). Such 
studies should provide new insights into mechanisms 
of hormonal carcinogenesis. 



Interagency Activities 

NIEHS continues to support the Environmental 
Mutagen Information Center at the Oak Ridge National 
Laboratory by interagency agreement. The center 
works closely with investigators around the world in 
both obtaining and supplying information on environ- 
mental mutagenesis. The center has over 30,000 
bibliographic entries in its data banks and remains a 
unique worldwide resource for information in the area 
of environmental chemical mutagenesis. 

NIEHS has also established the Environmental 
Teratology Information Center in collaboration with the 
Department of Energy and the Oak Ridge National 
Laboratory. Information on teratogenesis is collected, 
indexed, and made available to the biomedical com- 
munity directly from the center or the National Library 
of Medicine's TOXLINE. The center is a unique 
worldwide resource for information in the area of 
teratology. 



82 



14 



NATIONAL INSTITUTE OF 

NEUROLOGICAL AND 

COMMUNICATIVE 

DISORDERS AND STROKE 



Introduction 

The National Institute of Neurological and Communica- 
tive Disorders and Stroke (NINCDS) serves as the 
segment of NIH responsible for basic and clinical 
research on disorders of the nervous system and of 
human communication. Through its research grant 
program, application of Public Law 480, which permits 
use of U.S. -owned funds in the currencies of certain 
countries, and collaborative research projects engaging 
NINCDS scientists and their foreign colleagues, the 
Institute maintains continuing interaction with neuro- 
scientists internationally. The neurological and com- 
municative disorders are major problems in virtually 
every country of the world, and all nations stand to 
benefit from international research efforts and ex- 
change of knowledge. Furthermore, some of the 
neurological disorders vary in incidence and severity 
from country to country. Study of these variations, and 
uncovering of their causes, can be expected to lead to 
clearer understanding of the causes of the disorders 
themselves. The potential impact of international 
neuroscience research is therefore very great. 

Summary of Bid International 
Programs and Activities: Bilateral 
Agreements and Other 
Country-to-Country Activities 

In FY 1981, NINCDS participated in no bilateral 
agreements. Negotiations were initiated with the 
Government of Italy for epidemiological studies of 
stroke and the dementias. 

Egypt 

Two Egyptian projects were conducted on perinatal 
screening of developmental malformations and the 
venoms of poisonous snakes. In the perinatal screening 
project, over 10,000 patients in Cairo and Mansura have 
now been studied, and the project has revealed a 
higher-than-normal incidence of spina bifida and 
anencephaly. Data from this project are undergoing a 
comprehensive analysis to see if the reasons for the 
higher incidence can be determined. The snake venom 
study, involving collection of venoms from North and 



East Africa as well as Egypt, has resulted in the 
publication of six scientific papers in journals outside of 
Egypt, and has put the Egyptian Government in a 
position to manufacture good antivenins for North and 
Central Africa. 

Poland 

In 1981, NINCDS had four P.L.-480 projects funded at a 
total annual level of $269,000. Two in Poland were 
concerned with neuromuscular disorders: a study of the 
role of neuroglial cells in the processes of myelination 
and demyelination, and a study of the degree of muscle 
lesion in different disease conditions, and the connec- 
tion between endocrine and muscle disturbances. The 
Polish groups, located at the Medical Academy of 
Warsaw and at the Medical Academy in Poznan, have 
access to virtually all cases of neuromuscular disease in 
Poland, and are a valuable international research 
resource. 



Activities with International Agencies 

World Health Organization 

Since 1975, the NINCDS has been one of eight WHO 
Collaborating Centers in the Neurosciences. These 
centers, positioned strategically throughout the world, 
further international research efforts on neurological 
disorders and initiate and demonstrate community 
programs for prevention and treatment of these 
disorders. Special emphasis is being given to the 
cerebrovascular disorders (stroke), the convulsive dis- 
orders (epilepsy), and the neurological and com- 
municative disorders aspects of nutritional and de- 
velopmental problems of children. The other seven 
WHO Collaborating Centers in the Neurosciences are: 

•The Instituto Nacional de Neurologica, Mexico City, 

Mexico 

•The Montreal Neurological Institute, Montreal, 

Canada 

•The Groupe Hospitalier de la Timone, Marseilles, 

France 

•The University of Geneva, Geneva, Switzerland 

•The University of Ibadan, Ibadan, Nigeria 

•The Academy of Medical Sciences of the U.S.S.R., 

Moscow, U.S.S.R. 



83 



•The Nair Hospital and TN Medical College, Bombay, 
India 

Each center funds its own activities and includes 
collaborative research, publications for scientific in- 
formation exchange, support of conferences and 
courses, advisory services and technical assistance, and 
training. 

Health Scientist Exchange Programs and NIH 
Visiting Program 

During FY 1981, the NINCDS Intramural Program 
hosted 80 Visiting Scientists, Visiting Associates, and 
Visiting Fellows from 32 other countries. Countries 
represented were: 



Argentina 

Austria 

Belgium 

Bolivia 

Brazil 

Canada 

Denmark 

Finland 

France 

Greece 

Hong Kong 

Hungary 

India 

Iran 

Israel 

Italy 



Japan 

Korea 

Mexico 

Netherlands 

Nigeria 

People's Republic of China 

Philippines 

Poland 

Sierra Leone 

Spain 

Sweden 

Syria 

Taiwan 

Turkey 

United Kingdom 

Yugoslavia 



The contributions of these workers add immeasur- 
ably to the strength and effectiveness of the NINCDS 
Intramural Program, and the experience and new 
knowledge they take back with them to their home 
countries strengthen the neurosciences around the 
world. 

Extramural Programs 

NINCDS funded 13 foreign research grants in FY 1981, 
totaling $1,798,546. Grants were awarded to institu- 
tions in Canada, Israel, England, Sweden, Italy, and 
Mexico. These grants are for both clinical and basic 
research, and have been awarded to outstanding 
investigators exploring problems of high priority in the 
U.S. and in their own countries. 

The largest NINCDS foreign grant in 1981 was to 
the University of Western Ontario for the gathering and 
analysis of data from approximately 60 U.S. foreign 
medical centers on the effectiveness of a surgical 
procedure for preventing strokes. The procedure, 
involving grafting of a scalp artery to an intracranial 
artery to improve blood supply and known as the 
extracranial/intracranial bypass, is widely practiced but 
not statistically proven to be better than other forms of 
treatment. By 1983, the results of this study will be 
available to neurosurgeons and stroke specialists in all 
countries. 

NINCDS, the Fogarty International Center, and 
the WHO jointly sponsor a Neurosciences Fellowship 
Program. This program provides men and women from 



developing countries with stipend support for ad- 
vanced training in the U.S. to prepare them for 
leadership roles in academic and public health careers 
in the neurosciences in their own countries. In 1981, 
NINCDS supported three international neurosciences 
fellows, two at NIH from the People's Republic of 
China, and one at UCLA from the Philippines. 



Conferences, Seminars, and Meetings 
Sponsored by NINCDS 

In November 1980, NINCDS sponsored an internation- 
al meeting in Los Angeles on status epilepticus. The 
meeting resulted in formulation of guidelines for 
emergency room treatment of status epilepticus, and 
confirmed the potential usefulness of Lorazepam, a 
drug now undergoing development, which may im- 
prove the treatment of status epilepticus. 

Intramural Programs and Activities 

NINCDS' intramural work in epilepsy drug develop- 
ment has been greatly enhanced by collaboration with 
European drug firms, and in some cases, other foreign 
investigators. In 1981, this work continued, using 
progabide, an experimental antiepileptic drug manu- 
factured by a firm in France. NINCDS scientists also 
completed planning for a pilot study of flupertine, an 
experimental antiepileptic drug manufactured in West 
Germany. 

The extensive international collaborative work of 
the NINCDS Laboratory of Central Nervous System 
Studies on the slow, latent virus-induced brain dis- 
orders such as Creutzfeldt-Jakob disease and on Korean 
hemorrhagic disease and related disorders, which are 
endemic in Asia and portions of Europe, continued in 
1981. 

Part of this work is being carried on at a field 
research center established on Guam where a form of 
amyotrophic lateral sclerosis (ALS) is over 100 times 
more common than in the continental United States. 
Field surveys to obtain materials for further serologic, 
hematologic, neuropathologic, and genetic studies are 
being conducted. Originally, ALS was thought to be a 
genetically determined, inherited disease, but mount- 
ing evidence seems to indicate that some environmental 
factor may be responsible. Extensive analyses of family 
histories in a village (Umatac) where prevalence is 
extremely high are nearing completion. 

Discovery of a second focus of the disorder in the 
Kii Peninsula of Japan has heightened NINCDS efforts, 
in cooperation with other scientists, to ascertain the 
pattern of ALS distribution in the West Pacific islands 
and to evaluate as far as possible all suspicious 
environmental factors, including geographic, socioeco- 
nomic, dietary, and occupational features. An abnor- 
mally high incidence of Parkinsonism-Dementia Com- 
plex (a form of progressive extrapyramidal disease) has 
also been noted in this region. These and other 
neurosensory disabilities are under investigation in this 
unique environment. 



84 



15 



NATIONAL LIBRARY 
OF MEDICINE 



Introduction 

The International Programs of the National Library of 
Medicine (NLM) are a natural extension of NLM's 
domestic responsibilities. These activities are coopera- 
tive in nature and have relevance to both the developed 
and developing world. This past year has seen a 
continuation of the international MEDLARS agree- 
ments with the addition of a new center in Colombia; 
the continuing assessment of the NLM experimental 
program with the World Health Organization for the 
provision of services to developing countries; continua- 
tion of the NLM publications exchange program; the 
implementation of a cooperative program with the 
People's Republic of China; the production of critical 
reviews under the Special Foreign Currency Program; 
and specialized training for colleagues from abroad. 

Biomedical and health information is essential for 
the advancement of biomedical research, education, 
and the provision of health care. The recognition of this 
is evident in the international technical bilateral 
arrangements of NLM and the use of the MEDLARS 
system in many corners of the world. The mechanisms 
may be through on-line networks, linking the user to 
the computer system, or through NLM publications. 
The latter may be comprehensive, such as INDEX 
MEDICUS, or may be specialized, such as the Quarterly 
Bibliography of Major Tropical Diseases, but all serve the 
needs of the health professional. 

International MEDLARS Agreements 

The agreements for access to NLM's MEDLARS system 
are technical arrangements that are quid pro quo in 
nature. The cooperating country designates an institu- 
tion to serve as a national biomedical and health 
information resource. In return for MEDLARS tapes or 
telecommunications access to NLM's computer, the 
cooperating country performs or funds services to be 
provided to NLM. 

The new MEDLARS center at Colombia was 
established in 1981. The participating organizations in 
Colombia are the FUNDACION OFA para el Avance de 
las Ciencias Biomedicas and the Fondo Colombiano 
para Investigaciones Cientificas y Proyectos Especiales 
(COLCIENCIAS). FUNDACION OFA has as its objec- 
tives the improvement and accessibility of information 



for the biomedical professions and the improvement of 
the quality of education in the health sciences. An 
agreement was also reached between the National 
Library of Medicine and the Ministry of Health of 
Kuwait for the future implementation of a MEDLARS 
arrangement. 

Cooperation with the Chinese 
Academy of Medical Sciences 

The National Library of Medicine has a cooperative quid 
pro quo arrangement with the Institute of Medical 
Information, Chinese Academy of Medical Sciences. 
This arrangement was implemented in February of this 
year with the arrival of two Chinese scientists to work 
for approximately 5 months on the Chinese traditional 
medical literature in the collection of the NLM. The 
scientists identified, verified, and described almost 900 
items in such a way that the information is entered in 
the cataloging records and the computer system of the 
National Library of Medicine and made available to 
scholars. In return for their work on NLM's Chinese 
literature collection, the Library will provide two 
Chinese with training in modern medical library 
management and indexing. 

These two scientists brought special expertise to 
this task. One is an internist at the Capital Hospital 
(formerly Peking Union Medical College) of the Chinese 
Academy of Medical Sciences. Her experience has been 
in clinical work, teaching, research, and medical 
administration. She has been active in cooperative 
research programs which have combined both tradi- 
tional and Western medicine. 

The other is a traditional Chinese medicine physi- 
cian who is currently an Associate Research Fellow in 
the Department of Medicinal History and Literature of 
the Academy of Traditional Chinese Medicine. He has 
conducted research in Chinese medical history, the 
history of acupuncture and moxibustion, the history of 
Chinese materia medica, and ancient Chinese medical 
literature. He has been also a professor at the Advanced 
School of Traditional Chinese Medicine in Beijing, a 
member of the Editorial Committee of the Journal of 
Traditional Chinese Medicine, and was formerly Editor-in- 
Chief of the Chinese Quarterly of Acupuncture and 
Moxibustion. He has also conducted research on histor- 



85 



ical relics, including ancient scrolls, medical instru- 
ments, and medical stones. 



ment of Comparative Neurology at the Polish Academy 
of Sciences. 



Special Foreign Currency Program 

The Library's Special Foreign Currency Program, 
authorized by Public Law 83-480, as amended, made 21 
new awards during FY 1981. Under this program, 
appropriations of U.S. -owned local foreign currencies 
are available for scientific writing projects in coopera- 
ting countries, including Egypt, India, Israel, Pakistan, 
Poland, and Yugoslavia. The program is also currently 
funded through collaborative, bilateral agreements in 
Israel and Poland. This program enhances the Library's 
ability to procure and disseminate published informa- 
tion which is important to the progress of biomedical 
sciences and public health, using foreign scientific 
personnel and resources. 

The projects are multiyear; during FY 1981, there 
were 89 active projects, totaling an equivalent of 
$1,202,123 in foreign currencies. More than 50 percent 
of the program is currently carried out in Egypt and 
Poland; about 20 percent is carried out in India. New 
critical reviews and monographs in health fields 
constitute 45 percent of the projects; foreign translation 
projects represent another 28 percent. Of these 89 active 
projects, 25 are translations from Russian, and 11 from 
German. 

Included among the projects in the six cooperating 
countries are the preparation of critical reviews of 
biomedical research and practice; the translation of 
significant current and historical monographs in the 
biomedical sciences; publication of major international 
symposia and conference proceedings; and publication 
of authoritative bibliographies and other literature tools 
in special public health fields. These projects span a 
very broad subject range, with some of the major areas 
being history of medicine; cancer; heart disease; 
psychology; and physiology. Examples of new projects 
activated in FY 1981 include a translation of a Russian 
study on the neurophysiological investigation of a 
systems mechanism of behavior; a historical study, by a 
leading Egyptian scholar, of the health of the pharaohs; 
and the publication of a bibliography on ticks and 
tick-borne diseases. 

Among the studies published in FY 1981 under this 
proram was The Effects of Various Diseases on the 
Development of Atherosclerosis (New York, Pergamon 
Press, 1981). This book is the second major translation 
produced under the collaboration on cardiovascular 
disease within the U.S.-U.S.S.R. joint program and the 
NLM Special Foreign Currency Program. It presents 
original research on atherosclerosis conducted in the 
Soviet Union. The book was edited by a Harvard 
Medical School scientist, and printed in India. Another 
significant study is Tissue Neuropathology on Viral and 
Allergic Encephalitid.es (Warsaw, Poland, 1980). Distri- 
buted through the National Technical Information 
Service (NTIS), this book is a critical review of the world 
literature on the pathomorphology of viral and allergic 
encephalitis, with some emphasis on those types of 
encephalitis with which the late author worked person- 
ally in Poland as founder and director of the Depart- 



World Health Organization 

The National Library of Medicine and the WHO Special 
Program for Research and Training in Tropical Diseases 
continued to cooperate in the publication of a Quarterly 
Bibliography of Major Tropical Diseases. NLM produces 
this bibliography from the MEDLINE system, and 
WHO distributes approximately 5,000 copies to scien- 
tists in institutions in tropical countries. The diseases 
included in the bibliography are those identified by 
WHO for special attention: filariasis, leishmaniasis, 
leprosy, malaria, schistosomiasis, and trypanoso- 
miasis. 

An experimental program was continued between 
NLM and WHO for the provision of MEDLARS 
searches and interlibrary loans (photocopies of journal 
articles) to developing countries of the WHO Regions of 
Africa, Southeast Asia, the Eastern Mediterranean, and 
the Western Pacific. Under these arrangements, WHO 
has supported the equivalent of one and one-half 
people in residence at NLM. The level of activity is 
modest and its does respond partly to existing needs. 
However, it also emphasizes that developing countries 
continue to have significant requirements for biomedi- 
cal and health information which remain unsatisfied. 

Pan American Health Organization 

The National Library of Medicine's Assistant Director 
for International Programs serves as a member of the 
Scientific Advisory Committee for the PAHO Regional 
Library of Medicine (BIREME). Located in Sao Paulo, 
Brazil, BIREME is unique in the world as a regional 
resource. BIREME responded to 43,000 interlibrary loan 
requests, provided services from its subset of the 
MEDLINE database, held two training courses for Latin 
Americans, produced a Latin American INDEX MEDT 
CUS, and fostered networking within Brazil and among 
Latin countries. 

NLM MEDLARS Centers 



Tapes 


Tapes/Software 


On-line NLM 


Germany* 


Australia 


Canada 


Japan 


PAHO 


Colombia 




Sweden* 


France 




United Kingdom* 


Italy 

Kuwait** 
Mexico 
South Africa 
Switzerland 



Supplemental on-line access. 
Agreement signed but not operational. 



Visitors and Specialized Training 

The National Library of Medicine continues to receive 
about 1,000 international visitors yearly. These indi- 



86 



viduals represent both developed and developing information programs, and the establishment of nation- 
countries, and their interests include biomedical and al resources. Formal delegations were received from 
health research, medical education, health care in- France, India, Nigeria, the People's Republic of China, 
formation, library science, biomedical and health and Sweden. 



87 



16 



CLINICAL CENTER 



Introduction 

The Clinical Center (CC) was authorized by Congress to 
provide high-quality patient care necessary to conduct 
biomedical research. The 546-bed hospital has facilities 
and support services for nearly 1,000 physicians who 
conduct clinical research for 8 of the 11 NIH Institutes 
and for the National Institute of Mental Health (NIMH) . 
It was specially designed to place patient care facilities 
close to research laboratories to promote the quick 
transfer of new findings of basic and clinical scientists to 
the treatment of patients. Institutes admit to their units 
only those patients (upon referral by their personal 
physicians) who have the precise kind or stage of illness 
under investigation by scientist-clinicians. 

The Clinical Center ensures the highest possible 
level of medical care to each patient; provides optimal 
resources and facilities for clinical research; performs 
research on methods and systems involved in patient 
care and study; disseminates information to profession- 
als and to the public relevant to clinical investigation; 
develops and maintains training programs in the 
techniques and ethics of biomedical and clinical re- 
search; and interacts with scientists and physicians, 
nationally and internationally, on mutual problems of 
clinical research such as policy, education, ethics, and 
priorities. 

Intramural Programs and Activities 

Two scientists from the National Institute of Child 
Health and Human Development (NICHD) have been 
involved in a project over the past 4 years, in 
collaboration with scientists at the University of 
Athens, the Ben Gurian University School of Medicine 
in Be'er Sheba, Israel, and the Share Zadek Hospital in 
Jerusalem, Israel, to evaluate the use of vitamin E as an 
oral antioxidant in hereditary disorders of red cell 
metabolism with increased susceptibility to oxidant 
stress. The primary focus of this project has been on 
glucose-6-phosphate dehydrogenase (G6PD) deficien- 
cy, a disorder prevalent among both Mediterranean and 
African populations which affects approximately 300 
million people on a worldwide basis. Individuals with 
this disorder are subject to mild chronic hemolysis and 
acute episodic hemolysis which may often be life- 
threatening. In addition, G6PD deficiency may cause 



jaundice during the neonatal period which may require 
exchange transfusion and may affect subsequent neuro- 
logic development of individuals with this genetic 
disorder. 

Two other scientists, one a Belgian pediatrician and 
the other a clinical chemist, have collaborated on 
defining the role of one form of creatine kinase as an 
indicator of myocardial injury and as a tumor marker. 
Their goal is to determine what clinical value, if any, 
there is for the creatine kinase in diagnosing acute 
myocardial infarction, and as a marker for cancers 
involving tissues containing it. They have looked in 
particular at lung, prostate, and colon cancer. This form 
of creatine kinase may turn out to contribute to the 
management of patients in these two areas. 

Bilateral Agreements and Other 
Country-to-Country Activities 

Reciprocal visits of Soviet and Japanese physicians and 
scientists occurred during the past year. These were 
part of international programs for exchange of informa- 
tion relating to blood transfusion and viral hepatitis and 
for establishment of cooperative scientific studies. A 
study of viral hepatitis markers in Soviet and American 
blood donors was recently published as a result of this 
cooperation. 

Health Scientist Exchange 

A Visiting Scientist has been brought to NIH under 
guidelines for expert consultants. He is an established 
expert in the area of viral hepatitis and brings to the 
Blood Bank immunologic and biochemical knowledge 
and skills not otherwise available. His studies are aimed 
at developing a detection method for the non-A, non-B 
virus. This virus now accounts for over 90 percent of 
posttransfusion hepatitis (PTH) cases. A sensitive 
system for detecting the non-A and non-B virus in 
asymptomatic blood donors could dramatically de- 
crease the incidence of PTH, a disease which now 
occurs in approximately 300,000 blood recipients per 
year. 

Conferences, Seminars, and Meetings 

The Blood Bank has helped organize and sponsor the 
1981 International Symposium on Viral Hepatitis held 



89 



in New York City in March 1981, and cosponsored the themia. The latter sponsorship emanated from previous 
Second Conference on Regulation of Hemoglobin Blood Bank studies on high altitude disease, which 
Switching and a Conference on High Altitude Polycy- were conducted in Peru. 



90 



17 



DIVISION 

OF COMPUTER RESEARCH 

AND TECHNOLOGY 



Introduction 

The Division of Computer Research and Technology 
(DCRT) was established in 1964 to make the use of 
computational methods a tool for the NIH biomedical 
community. Over the years, the work of the Division 
has become an integral part of the conduct and 
management of NIH research programs. At the same 
time, DCRT has grown to become the largest biomedical 
computing facility in the world. DCRT staff members 
continue to create still more powerful and useful 
systems. Their challenges lie in building strong intellec- 
tual links from computers, mathematics, and engineer- 
ing to the substance of science and the art of 
administration. 

Summary of Bid International 
Programs and Activities 

Four foreign scientists worked at the Division during FY 
1981: two from Israel (Physical Sciences Laboratory), 
one from Belgium (Laboratory of Applied Studies), and 
one from Mexico (Laboratory of Statistical and Mathe- 
matical Methodology). 

In addition, the Division cosponsored, with the 
European Society of Cardiology and others, Computers 
in Cardiology. This annual conference provides a forum 
for physicians, engineers, and computer scientists to 
exchange scientific information on the design and 
application of computer systems to the field of car- 
diology. 

DCRT staff members informally collaborated with 
scientists from foreign countries including Australia, 
Scotland, Japan, France, Canada, Switzerland, Ghana, 
Greenland, and Singapore. Examples of these interna- 
tional collaborations included: 
•Computer- Aided Analysis of Electrocardiograms 
Glasgow Royal Infirmary, Glasgow, Scotland 
University of Liege, Belgium 



P. L. Medical Service Department, Osaka, Japan 
Centre du Medicine Preventive, Nancy, France 
•Analysis of Coupled Transport and Biochemical 
Kinetics 

Universite de Technologie, Compiegne, France 
•Automated Data Processing of Medical Language 
Mexico 

•Multivariate Statistical Analysis 
University of Western Australia, Nedlands, Australia 
Flinders University, Adelaide, Australia 
•Computer Support for Flow Microfluorimetry/Cell 
Sorters (FMF) 

Sites in Europe and Australia 

•Chinese Personalities and Institutions in Biomedicine 
Fogarty International Center project for the People's 
Republic of China 

•Theory and Measurement of Intermolecular Forces 
Guelph University, Guelph, Ontario, Canada 
•Theory of Biochemical Separation Techniques 
University of Sydney, Sydney, Australia 
•Quantitative Analysis of the Electronmicroscopy of 
Cells and Their Plasma Membranes 
University of Geneva, Geneva, Switzerland 
•Multivariate and Univariate Forecasts for Blood Con- 
stituents 

Health Maintenance Program, Japan 
•Seroepidemiology Data Processing System 
Scientists in Ghana, Greenland, and Singapore 

Foreign scientists from West Germany, France, 
Japan, and the People's Republic of China came to 
DCRT to draw upon the expertise of its computer 
scientists. The American Association for the Advance- 
ment of Science brought a delegation of international 
representatives from the Philippines, the Soviet Union, 
and Hungary for a look at the establishment of the 
facility for biomedical computing at NIH, as a model. 

DCRT supported, and its scientists took part in, 
several international conferences and meetings during 
FY 1981. 



91 



18 



DIVISION OF 
RESEARCH RESOURCES 



Introduction 

Most international activities of the Division of Research 
Resources (DRR) fall under the Animal Resources 
Program (ARP), which has the overall objective of 
supporting resource projects that provide or enable 
scientists to use animals effectively in human health- 
related research. Special attention is given to animal 
resource activities that are broadly supportive of the 
missions of the various NIH Institutes. The objectives 
are accomplished through the Primate Research Cen- 
ters Program (PRCP) and the Laboratory Animal 
Sciences Program (LASP). Both of these programs, 
either directly or through grants, are internationally 
involved in various facets of primatology interest. 

Summary of Bid International 
Programs and Activities: Activities 
with International Agencies 

The Simian Virus Reference Laboratory at the South- 
west Foundation for Research and Education, San 
Antonio, Texas (LASP grantee) has been designated by 
the World Health Organization (WHO) as a Collabora- 
ting Center for Reference and Research in Simian 
Viruses. The primary purposes of this laboratory are: to 
prepare, test, evaluate, and standardize simian virus 
reagents; to provide definitive virus diagnostic services, 
including identification and characterization of viruses 
that may be present in primate tissues; to provide 
consultation services and encourage pooling of in- 
formation and exchange of organisms among primate 
centers and other health organizations; and to train 
interested students in virological laboratory procedures 
associated with primate investigations. 

Extramural Programs 

ARP supports a project which studies important habitat 
features of West African rain forest primates. This 
project involves a detailed examination of the rela- 
tionship between feeding behavior, specific ecological 
conditions, and social organization. It is essentially a 
predictive study, in which such important variables as 
foraging styles, diet selection, home range, group size 
patterns, population density, distribution, and social 



interaction are expected to relate in specific ways to 
ecological conditions. The information will be useful, 
not only to behaviorists, sociologists, and botanists, but 
also to conservationists and those making decisions 
about the size of forest areas in Africa that are necessary 
to maintain wild populations of primates. 

ARP supports a project in northern India focused 
on population studies of nonhuman primates. The 
project, begun in 1959 (supported by ARP since 1973), 
has provided data regarding population dynamics and 
demographic and reproductive parameters of a natural 
rhesus monkey population. Within the study, popula- 
tion declines of 71 percent (up to 1977) were noted in an 
unprotected cohort while a semiprotected cohort in- 
creased 186 percent in the same period. Ongoing 
studies will provide data on the effects of the current 
export ban of rhesus monkeys from India, habitat 
displacement which is occurring with one study group, 
and the feasibility of intentional transplants and 
relocation of breeding groups. Such information is 
necessary as a guide to conservation and management 
of rhesus monkeys and will be important in evaluating 
the potential supply of rhesus monkeys for biomedical 
research. 

PRCP partly supports a project for the Kutai 
Research Station in Indonesian primate conservation 
methodology. Surveys of the natural populations of 
primate species have been conducted, and training in 
conservation methods has been provided to ensure the 
continued availability of supplies of Macaca nemestrina 
and Macaca fasicularis for use in biomedical research. 

The Institute of Primate Research of the National 
Museums of Kenya, conceived many years ago by the 
late anthropologist Dr. Louis Leakey, has recently 
achieved the status of a Kenyan International Primate 
Research Center. PRCP provides partial support for its 
program which consists of the following activities: 
baseline studies on African primate species; develop- 
ment of primate models for atherosclerosis research; 
infectious diseases research; coordination of primate 
field studies; and collaborative research with Kenyan 
and foreign scientists. The center's overall goal is to 
contribute to knowledge about East African primate 
species while fulfilling research needs of Kenya and 
other countries. The center is being relocated to a new 
100-acre site near Nairobi, where construction of 
facilities is currently underway. 



93 



19 



DIVISION OF 
RESEARCH SERVICES 



Introduction 

Through collaboration and cooperation with national 
and international organizations, the Division of Re- 
search Services (DRS) plans and conducts centralized 
programs of scientific, engineering, and technical 
services in support of biomedical research activities. 
Professional and technical staff members consult with 
research scientists during all stages of a research project 
for the development and use of essential products and 
services. DRS personnel provide specialized assistance 
and services in biomedical engineering and instru- 
mentation design and development; research animal 
production, maintenance, procurement, and animal 
disease identification and control; biomedical library 
and translation services; and medical arts and photo- 
graphy. 

DRS is involved internationally in such issues as 
developing a primate supply program for biomedical 
research; establishing training programs in conserva- 
tion and management of wild primates; supplying 
organizations and institutions throughout the world 
with genetically defined rodents as nuclei for colony 
development; sponsoring the development of methods 
for primate population studies and surveys; and 
initiating programs to train scientific instrument techni- 
cians and to establish repair and maintenance centers. 

Bilateral Agreements and Other 
Country-to-Country Activities 

Egypt 

The Biomedical Engineering and Instrumentation 
Branch (BEIB) is cooperating in two projects with the 
Egyptian Government to improve Egypt's capability to 
repair scientific and hospital equipment. 

The first project, funded by the United States 
Agency for International Development (USAID) with 
the Egyptian Academy for Scientific Research and 
Technology, is to establish repair and maintenance 
facilities at five Egyptian universities. During the first 
phase of this project, which will end January 31, 1982, 
BEIB has assisted in the design of the individual repair 
centers, trained administrative personnel, fully equip- 
ped each center, and trained a few personnel for each 
center in the repair and maintenance of scientific and 
hospital equipment. During the second phase of this 
project, BEIB will assist the Egyptian Government in 



developing a self-sustaining program in Egypt for the 
training of repair and maintenance personnel and the 
development of a nationwide program for the repair 
and maintenance of scientific equipment. 

The second project, funded by USAID and Special 
Foreign Currency Program funds, is with the Egyptian 
Ministry of Health. This project, which is at its 
mid-point, is to establish a prototype repair and 
maintenance program for an Egyptian governorate 
which will be used as a model for other programs to be 
established throughout Egypt. BEIB has assisted the 
Ministry of Health in supplying the center with the 
necessary equipment and spare parts, and has to date 
trained two Ministry of Health personnel in the repair 
and maintenance of scientific and hospital equipment. 
The center, to be located in the governorate of Giza, is 
scheduled to open January 1, 1982. 

Japan 

As a result of a proposal by the U.S. -Japan Counterpart 
Working Group, which met as part of the U.S. -Japan 
Meeting on Research Cooperation in Science and 
Technology in February 1980, an international agree- 
ment between the two Governments was finalized 
which included a collaborative project in laboratory 
animal science. The agreement is entitled Agreement 
Between the Government of Japan and the Government 
of the United States of America on Cooperation in 
Research and Development in Science and Technology, 
April 14, 1980 (U.S. -Japan Non-Energy Cooperative). 
The purpose of the project is to promote the exchange of 
information on laboratory animal models, the develop- 
ment and use of uniform international standards for 
research animals, and the exchange of information on 
other aspects of laboratory animal science. The Division 
of Research Services was given responsibility for U.S. 
involvement in this project. 

In May 1980, a joint meeting was held in the U.S. to 
plan for cooperation and future development of 
activities in the laboratory animal science project. It was 
decided that the initial thrust should be toward 
information on quality control of laboratory animals. 
The group agreed to encourage a series of workshops to 
pursue these topics with an ultimate goal of preparing a 
series of U.S. /Japan Laboratory Animal Quality Control 
manuals. The first workshop was conducted on genetic 
monitoring and was held in Tokyo in July 1980, with 
active participation by representatives from both coun- 



95 



tries. A manual on genetic monitoring is nearing 
completion. In December 1980, the Japanese hosted the 
first meeting on microbiologic monitoring of laboratory- 
animals. The United States will host a second meeting 
in San Francisco, December 14-16, 1981, to begin 
drafting a manual on monitoring of selected microbial 
agents that interfere with the use of laboratory rodents 
in biomedical research. 

Activities with International Agenices 

World Health Organization 

The NIH genetic resource of laboratory rodents and 
rabbits has been designated as a WHO Collaborating 
Center for Defined Laboratory Animals, and as an 
international nude mouse reference center by the 
International Council on Laboratory Animal Science 
(ICLAS). The resource maintains over 200 stocks and 
strains of genetically and microbiologically defined 
rodents and rabbits and serves as a source of breeding 
nuclei of animals used by NIH research investigators as 
well as the international biomedical research communi- 
ty. Over 5,000 animals were supplied to domestic and 
foreign research institutions in FY 1981. 

In late FY 1980, a contract was awarded to the 
World Health Organization (WHO) to develop an 
international primate supply program. WHO is to 
provide expert consultation and advisory assistance to 
the governments of interested countries in planning 
and implementing conservation measures, and ensur- 
ing the continuing availability of nonhuman primate 
species necessary for biomedical research. This contract 
is intended to implement recommendations made by 
the Interagency Primate Steering Committee as out- 
lined in the National Primate Plan. 

The National Institutes of Health (NIH) has a 
critical interest in the continuing supply of nonhuman 
primates. NIH intramural programs (including the 
Bureau of Biologies, FDA, needs of which are supplied 
through NIH) utilize more nonhuman primates than 
any other government organization. In addition, NIH 
extramurally supported research requires one-third of 
the total animals used for health-related programs. 
Another major user group is the 
pharmaceutical% biological industry, where nonhuman 
primates are required for the production and testing of 
drugs and biologic products that are licensed and 
controlled by the Food and Drug Administration. 
Because of the rapid decline of primate populations, 
and because of the importance of these animals to 
human, health-related needs, the objectives served by 
the WHO contract are of the utmost importance. It is 
hoped, through conservation management programs 
and the breeding of nonhuman primates under semi- 
natural conditions in countries where they are indige- 
nous, that surplus animals will be available for 
biomedical investigation without endangering native 
populations of animals. 



Pan American Health Organization 

The Interagency Primate Steering Committee, through 
a contract with the Pan American Health Organization 
(PAHO), has developed projects to establish New 
World primate breeding centers and conservation 
programs in Latin American countries. The majority of 
these countries imposed restrictions on the commercial 
export of nonhuman primates in 1973, and several have 
been interested in providing those species required for 
biomedical research through captive breeding and 
controlled wildlife management programs. 

Specific objectives of the contract are: 
•To provide expert consultants and advice to Latin 
American Governments interested in developing 
national primate programs as recommended by the 
World Health Organization; 

•To assist in developing programs of wild primate 
conservation and management; 

•To ensure the perpetuation of natural nonhuman 
primate resources; and 

•To support development of primate breeding stations 
to produce species important to biomedical research 
under captive or semicaptive conditions. 

The fully established Peruvian National Primate 
Project includes a breeding station in Iquitos, as well as 
field management activities. Tamarins and squirrel 
monkeys have been provided for use in U.S. biomedical 
activities since 1976. As a result of an agreement 
between PAHO and the Government of Colombia, a 
captive owl monkey breeding station was established at 
Armero, and an ongoing conservation program is being 
developed. It is anticipated that an agreement will also 
be undertaken to assist in coordinating primate breed- 
ing and conservation programs in Brazil. These pro- 
grams will eventually become self-supporting through 
funds received for primates that are made available for 
scientific use. 

Scientific Attache and International Health 
Representative to India 

In January 1980, a senior staff member was detailed to 
the Department of State and has been assigned to the 
U.S. Embassy in New Delhi, India, as the U.S. Scientific 
Attache and International Health Representative. In 
this assignment, he assists the Scientific Counselor in all 
matters relating to U.S. scientific affairs in India, with 
specific responsibility for representing, monitoring, 
and coordinating the program interests of the U.S. 
Department of Health and Human Services and other 
U.S. agencies engaged in health and health-related 
activities. The appointment is important to the Depart- 
ment because of the interest in continuing collaborative 
health activities with India, particularly in view of the 
Department's policy to focus even greater attention and 
resources on health problems of the developing world. 



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NIH Publication No. 82-62 
September 1982